Search

The concentration of homovanillic acid and p-tyramine in the female corpus striatum were increased after ovariectomy. The increases were reversed by chronic administration of estradiol benzoate and potentiated by progesterone. It is proposed that these changes are the consequence of concomitant variations in p-tyrosine availability.

The decarboxylase inhibitor DL-alpha-monofluoromethyldopa reduces, in a dose dependent manner, the concentration of striatal p-tyramine in the mouse. Homovanillic acid is also significantly reduced. Conversely, this treatment increases the m-tyramine concentration. Administration of m-tyrosine produces large increases in m-tyramine and a slight decrease in p-tyramine; these changes are potentiated in the presence of the decarboxylase inhibitor. Such data along with other recently published results permit the conclusion that m-tyramine arises from phenylalanine via m-tyrosine and that p-tyramine arises by decarboxylation of p-tyrosine. Both these reactions are closely related to the activity of tyrosine hydroxylase and the availability of appropriate substrates.

The mouse brain contains 12.5 and 4.1 ng/g of p- and m-hydroxyphenylacetic acids, respectively. The hydroxyphenylacetic acids were isolated by chromatography on DEAE-Sephadex A-25 and quantitated as their pentafluoropropionyl and hexafluoropropanol esters by use of a gas chromatograph equipped with an electron-capture detector. The highest concentrations of p- or m-hydroxyphenylacetic acids were observed in the caudate nuclei (27.9 and 8.7 ng/g, respectively) and olfactory tubercles (20.2 and 5.3 ng/g, respectively). The identities of the p- and m-hydroxyphenylacetic acids were further confirmed as a consequence of the reductions observed following monoamine oxidase inhibition or the increases observed in the appropriate acid following the parenteral administration of p- or m-tyramine.

These experiments show that in the rat corpus striatum the highest concentrations of p- and m-tyramine were found in the caudate nucleus while somewhat lower values were observed in the putamen and globus pallidus. Inhibition of monoamine oxidase by pargyline produced an increase in the concentration of both tyramines in the three areas. The effect of pargyline is more marked with p-tyramine, however, the regional distribution of both p- and m-tyramine are preserved after monoamine oxidase inhibition. In addition, the pargyline treatment produced a significant reduction in corpus striatum p-tyrosine while no changes were observed in the tryptophan concentrations.

1. Insulin binding sites were characterized and quantified in snail (Helix aspersa) ganglia by incubation of tissue sections with 125I-porcine insulin, autoradiography with [3H]Ultrofilm, image analysis coupled to computer-assisted microdensitometry, and comparison with 125I-standards. Cellular localization was performed in the same sections by emulsion autoradiography. 2. Specific insulin binding sites were demonstrated in discretely localized groups of neurons of the cerebral, pleural, parietal, visceral, and pedal ganglia and in nerves. Scatchard analysis performed with consecutive sections from single animals revealed a single class of high-affinity insulin binding sites (Kd, 0.13 +/- 0.01 nM; Bmax, 157 +/- 10 fmol/mg protein). 3. Our results suggest that insulin may play a role as a neurotransmitter or neuromodulator in snail ganglia.

In spontaneously beating rat atria the potencies for the chronotropic effects of the following deuterated phenylethylamine derivatives were higher than the potencies of the corresponding non-substituted (protio-) amines: alpha,alpha,d2-beta-phenylethylamine; alpha,alpha,beta,beta-d4-p-tyramine; alpha,alpha,beta,beta-d4-m-tyramine; alpha,alpha,beta-d3-p-octopamine. In contrast, alpha,alpha,beta-d3-noradrenaline and alpha,alpha,beta-d3-m-octopamine were equipotent with the corresponding protio-amines. Experiments performed in atria depleted of endogenous noradrenaline by pretreatment with reserpine and in atria exposed to the monoamine oxidase (MAO) inhibitor pargyline indicated: a. p-octopamine had both direct and indirect effects, but the chronotropic responses to p-octopamine in tissues with normal MAO activity depended mostly on the direct action of the amine; deuterium substitution enhanced the indirect component of action of p-octopamine; b. m-octopamine possessed considerable indirect effects while d3-m-octopamine behaved as an amine of direct action. The substitution of deuterium for hydrogens in the alpha-carbon of the alkyl-side chain of phenylethylamines decreases the rate of deamination by MAO. Therefore, the results obtained with all the amines, except for m-octopamine and alpha, alpha,p-d3-m-octopamine, could be interpreted in terms of the direct, indirect or mixed action of those compounds and/or of the influence that MAO activity has on the chronotropic responses to these amines. The results obtained with protio- and deuterio-m-octopamine suggested that deuterium substitution, either at the alpha- or the beta-carbon, can alter some other mechanisms in addition to the enzymatic deamination.

Injection of L-p-tyrosine (800 mg/kg, 2 h) increased the mouse striatal para-hydroxyphenylacetic acid (p-HPAA) concentrations. A smaller dose of D,L-m-tyrosine (20 mg/kg, 2 h) produced a larger increase in mouse striatal meta-hydroxyphenylacetic acid (m-HPAA) concentrations. The administration of L-phenylalanine to mice caused a slight increase in the p-HPAA concentration in the corpus striatum after 2 h while a larger dose of L-phenylalanine (800 mg/kg) produced a greater increase. Eight hours following L-phenylalanine injection, p-HPAA concentrations were still elevated. With D-phenylalanine a significant increase was observed at eight hours after drug administration. Two drugs which reduce dopamine synthesis, alpha-methyl-para-tyrosine and apomorphine, decreased m-HPAA striatal concentrations without affecting p-HPAA concentrations. From these results, it is proposed that tyrosine hydroxylase activity determines p-HPAA concentrations by regulating p-tyrosine availability. This enzyme may also synthesize m-tyrosine which is subsequently decarboxylated to form m-tyramine and then oxidatively deaminated to form m-HPAA.

Phenelzine is a monoamine oxidase inhibitor with antidepressant properties. The present study investigated effects of acute (1-2 mg kg-1 4 h s.c.) and chronic (0.25-2 mg kg-1 day-1 Alzet miniosmotic pumps, 13 days s.c.) administration of phenelzine on regional monoamine metabolism in rats. The effects of these phenelzine treatments were compared with those of equivalent doses of a deuterated form of the drug (phenelzine-d4). The following brain regions and compounds were assessed using high performance liquid chromatography with electrochemical detection: Striatum: dopamine, DOPAC, HVA, 5-HT, 5-HIAA; hypothalamus: dopamine, 5-HT, 5-HIAA, noradrenaline; hippocampus: 5-HT, 5-HIAA, noradrenaline; frontal cortex: dopamine, noradrenaline, 5-HT, 5-HIAA. Acute drug administration increased levels of dopamine, 5-HT and noradrenaline with the exception of dopamine in the hypothalamus and frontal cortex and 5-HT in the hypothalamus. DOPAC, HVA and 5-HIAA levels were decreased. After chronic administration amine levels increased with the exception of dopamine administration amine levels increased with the exception of dopamine in the hypothalamus. The respective acid metabolites were also decreased. These effects of phenelzine were markedly potentiated by deuterium which was substituted for hydrogen in the side chain. The potentiation of these effects was enhanced with chronic administration, differences between phenelzine and phenelzine-d4 effects being more marked at lower doses.

Striatal amine levels were measured six weeks after unilateral injections of 6-OHDA (8 micrograms) into the substantia nigra in male Wistar rats pretreated with monoamine oxidase inhibitors. After (-) deprenyl.HCl pretreatment (2 mg.kg-1 SC 2hr), beta-phenylethylamine, m- and p-tyramine ipsilateral to the 6-OHDA lesion decreased to 50, 18 and 25% of contralateral levels. DA, DOPAC and HVA also decreased on the lesioned side. Ipsilateral concentrations of tryptamine, 5-HT, 5-HIAA, p-tyrosine and L-tryptophan concentrations were equivalent to contralateral values in this condition. In animals pretreated with pargyline.HCl (200 mg.kg-1 IP 2hr) m- and p-tyramine and tryptamine ipsilateral to the lesion decreased to 48, 59 and 57% of contralateral levels. Ipsilateral DA decreased to 26% of the contralateral value. Under these conditions no change in concentrations of beta-phenylethylamine or of the above acid metabolites or amino acids was observed. The masking of lesion-induced changes in beta-phenylethylamine by pargyline is attributed to the lipophilic nature of of this molecule and consequent diffusion of this amine from other areas after maximal monoamine oxidase inhibition. Conversely the failure to demonstrate lesion-induced changes in tryptamine with (-) deprenyl pretreatment is attributed to the nonselectivity of monoamine oxidase for tryptamine and activity of monoamine oxidase A under these conditions. These results indicate that for further assessment of lesion-induced changes in beta-phenylethylamie and of tryptamine the respective (-) deprenyl and pargyline pretreatments used in this study are appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of p-tyramine and p-octopamine on the twitch responses of the prostatic portion of the rat vas deferens to electrical stimulation (0.025 Hz) were compared with the effects of noradrenaline. In tissues with normal monoamine oxidase (MAO) activity, the three amines increased the height and duration of the twitch contractions. When MAO activity was inhibited by pargyline (10 mumol/l), p-tyramine and p-octopamine had mixed excitatory-inhibitory effects on the twitches, while noradrenaline had mostly excitatory effects along the whole range of concentrations assayed (0.158-15.8 mumol/l). Selective blockade of alpha 1- and alpha 2-adrenoceptors, by corynanthine and yohimbine, respectively, showed that the excitatory effect of the amines depended on the activation of alpha 1-adrenoceptor and that the inhibitory action was related to the activation of alpha 2-adrenoceptors. Pretreatment with reserpine (5 mg/kg, 24 h; 2.5 mg/kg, 2 h before the experiment) largely prevented the effects of p-tyramine and p-octopamine, but the amines still modified the twitch responses to field stimulation. The addition of corynanthine and yohimbine to the bathing fluid revealed a considerable activation of alpha 1-excitatory and alpha 2-inhibitory adrenoceptors. Cocaine (10 mumol/l) did not antagonize, but rather enhanced the inhibitory effects of p-tyramine and p-octopamine in tissues with normal contents of noradrenaline. Moreover, cocaine did not antagonize the inhibition caused by p-tyramine, and enhanced the inhibition induced by p-octopamine in the prostatic portion of the vasa deferentia from reserpine-pretreated animals. These results suggest that in this tissue, at least when MAO activity is inhibited, p-tyramine and p-octopamine behave similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

1 The concentrations of p- and m-tyramine were measured in the caudate nucleus of the rat brain following subcutaneous injection of reserpine or intraventricular injection of 6-hydroxydopamine, beta-Phenylethylamine was analysed in the hypothalamus after reserpine. 2 Endogenous levels of p-tyramine and m-tyramine in the caudate nucleus, and beta-phenylethylamine in the hypothalamus were 8.02, 2.25 and 2.52 ng/g respectively. 3 Tyramine concentrations were reduced to less than 20% of control values one day after a reserpine injection of 1 or 10 mg/kg. A single dose of reserpine (0.4 mg/kg) significantly decreased the content of both tyramines in the caudate nucleus. The effects became apparent as early as 45 min after drug case of m-tyramine. 4 The hypothalamic content of beta-phenylethylamine was unaffected by reserpine. 5 Ten days after an intraventricular injection of 6-hydroxydopamine (250 mug), p- and m-tyramine concentrations in the caudate nucleus were significantly below control levels. 6 The results suggest that p- and m-tyramine may be stored by an intraneuronal reserpine-sensitive storage mechanism. Alternatively, the tyramines may replace some of the catecholamines from their storage granules and then be released as false transmitters by the nervous impulse. The observed changes in tyramine levels might also the fact that these amines may be metabolically related to another amine which is stored in reserpine-sensitive granules.

1 The concentrations of p- and m-tyramine, dopamine and homovanillic acid were measured in the mouse striatum following the subcutaneous injection of gamma-hydroxybutyrate; their control levels were 19.8, 6.3, 9600 and 1130 ng/g respectively. 2 The administration of 500-1000 mg/kg of gamma-hydroxybutyrate produced a reduction in p-tyramine that lasted at least 8 h. m-Tyramine and dopamine were significantly increased for at least 4 h. The levels of homovanillic acid were increased at 1 and 2 h after drug administration. 3 There experiments strongly suggest that the increases in dopamine turnover produced by gamma-hydroxybutyrate caused reciprocal changes in striatal tyramine that are similar to those produced by drug or treatment that increase dopamine turnover and tyrosine hydroxylase activity.

The concentrations of p-tyramine (p-TA), m-tyramine (m-TA), dopamine (DA) and their principal metabolites, p-hydroxyphenylacetic acid (p-HPAA), m-hydroxyphenylacetic acid (m-HPAA) and homovanillic acid (HVA) were determined in the corpus striatum of Swiss mice at various times after the subcutaneous administration of beta-phenylethylamine (PE) (50 mg/kg). Initially p-TA concentrations were reduced but rapid synthesis was apparent up to 2 h after PE administration. PE treatment increased m-TA and these increases reached significance at 1 and 8 h. PE caused a bimodal increase in p-HPAA and m-HPAA concentrations with the first peak observed at 0.5-1 h due to initial release of p-TA and m-TA. Rapid synthesis of p-TA and m-TA resulted in increased acid concentrations at 4 h. HVA concentrations were increased up to 1 h after PE administration. The synthesis of p-TA and m-TA is related to that of DA probably as a result of the activation of tyrosine hydroxylase. PE may serve as a precursor for p-TA synthesis when the endogenous PE concentration is greatly elevated.

This is an investigation of the effects of electrolytic lesions (1 mA, 10s, anodal) on the median and dorsal raphé nuclei of Wistar rats on the striatal concentrations of p-tyrosine, p-tyramine, m-tyramine, DA, DOPAC, and HVA. The extent of the lesions was estimated in terms of the depletion of 5-hydroxytryptamine and 5-hydroxyindole acetic acid as well as histological examination of the lesioned area. The results show that the raphé nuclei lesions increased rat striatal levels of DOPAC and HVA while levels of DA were unaffected, an effect that was observed within the first day after the lesions were made. The increases in DOPAC and HVA were accompanied by a reduction in striatal p-tyramine and an increase in m-tyramine. The results further support the existence of a reciprocal relationship between p- and m-tyramine concentrations and dopamine metabolism. Previous experiments have demonstrated depletion of p-TA following nigral lesions. The present results are, therefore, important in relation to tyramine distribution in brain. The p- and m-tyramine concentrations were not reduced at 7 days after the raphé nuclei lesions indicating that if the striatal tyramine-containing neurons exist, they do not originate in or pass through the dorsal or median raphé nuclei.

The effects of phenelzine and 1,1-dideuterophenelzine (0.5 or 2.5 mg/kg/day) administered s.c. via miniosmotic pumps for 13 days were compared. Striatal levels of p-tryrosine and tryptophan were unaffected by either treatment. The concentrations of DOPAC, HVA and 5-HIAA were dose-dependently decreased by phenelzine and deuterated phenelzine; furthermore, the deuterated compound decreased the amounts of these acids more than the same dose of phenelzine. Dopamine levels were increased by a rather small amount by all drug treatments; no effects of drug dose or drug type (deuterated or nondeuterated) were observed. With the exception of phenylethylamine, qualitatively similar effects were found with all other amines measured; their amounts were increased dose-dependently and the effects of deuterated phenelzine were greater than those of phenelzine. Rat cerebral MAO activity was inhibited dose-dependently by phenelzine and by deuterated phenelzine. Type A MAO was inhibited more than type B, and deuterated phenelzine inhibited both types more than did phenelzine. The present study shows that the efficacy of phenelzine was increased about 5-fold by deuteration, that deuterated phenelzine increased tryptamine, m-tyramine and p-tyramine levels much more than it did the other monoamines, that phenylethylamine levels were least affected by the drug treatments, and that deuterated phenelzine inhibited MAO more than did phenelzine.

A number of phenylethylamines and indoleamines have been analyzed in the circumoesophageal ganglia and posterior salivary gland of the normal and pargyline-treated maleOctopus dofleini martini. β-Phenylethylamine,m-tyramine, and tryptamine are present in the optic lobes in amounts of 3, 0.6, and 0.6 ng/g, and in the posterior salivary gland at levels of 1, 64, and 52 ng/g, respectively, in contrast to the much higher levels observed forp-tyramine, octopamine, dopamine, noradrenaline, and 5-hydroxytryptamine. Although pargyline causes a substantial increase in the content of β-phenylethylamine,m-tyramine,p-tyramine, and tryptamine in the optic lobes, no significant changes are observed in the posterior salivary gland. Their relatively rapid metabolism suggests an active role for these amines in the function of nervous tissue in theOctopus.

The effects of lesions of the substantia nigra (electrolytic 2 mA 10 sec, or 6-OHDA 2 or 8 micrograms) and of the midbrain raphé nuclei (electrolytic 2 X 1.0 mA 10 sec) at 7 days postlesion on striatal levels of beta-phenylethylamine, DA, DOPAC, HVA, 5-HT and 5-HIAA and on hypothalamic levels of beta-phenylethylamine, DA, NA, 5-HT and 5-HIAA were investigated. In the presence of deprenyl (2 mg kg-1 2 hr SC), both electrolytic and 6-OHDA-induced dopamine-depleting lesions of the nigra but not 5-HT-depleting lesions of the raphé nuclei resulted in a marked decrease in the accumulation of beta-phenylethylamine. The marked reduction in accumulation of striatal beta-phenylethylamine in response to lesions of the substantia nigra indicates that the intraneuronal compartment is a major site of striatal beta-phenylethylamine synthesis. An equivalent decrease (approximately 40%) in the accumulation of 5-HT was observed following electrolytic lesions of the substantia nigra or raphé nuclei after administration of L-5-HTP (200 mg kg-1 hr IP). As L-5-HTP at the dose employed in this study is taken up non-selectively by both DA- and 5-HT-containing neurones the loss of L-AAD following nigral and raphé lesions was apparently equivalent. These results indicate that depletion of beta-phenylethylamine may not be simply attributable to a general loss of L-AAD following lesions of monoamine-containing neurones and suggest either co-localisation of beta-phenylethylamine and DA or the existence of distinct beta-phenylethylamine-containing neurones.

The addition of L-3,4-dihydroxyphenylalanine, L-5-hydroxytryptophan or m-tyrosine to cultured isolated astrocytes does not elicit the synthesis of either dopamine, 5-hydroxytryptamine or m-tyramine, respectively. In contrast, the astrocytes show ability to take up and store dopamine and 5-hydroxytryptamine that are in turn respectively metabolized to 3,4-dihydroxyphenylacetic acid or 5-hydroxyindoleacetic acid. These findings suggest that astroglial cell cultures lack aromatic-L-amino acid decarboxylase and give further evidence that these cells contain monoamine oxidase.

1 The concentrations of p- and m-tyramine, dopamine and homovanillic acid were measured in the mouse striatum following the subcutaneous administration of amfonelic acid, (+)-amphetamine or nomifensine.2 The administration of 2.5-25 mg/kg of amfonelic acid produced a reduction in p-tyramine that lasted at least 8 h. m-Tyramine was significantly increased and this was observed between 2 and 24 h after drug treatment. The levels of homovanillic acid were increased within 4 h after amfonelic acid administration.3 (+)-Amphetamine treatment (5 mg/kg) produced a reduction in p-tyramine observed up to 4 h after its administration and no significant changes in m-tyramine.4 The administration of 10 mg/kg of nomifensine produced no significant changes in p-tyramine, m-tyramine or homovanillic acid. By increasing the dose to 20 mg/kg, nomifensine produced an increase in p-tyramine and homovanillic acid.5 The present results support the view that amfonelic acid and (+)-amphetamine would respectively release granular or newly synthesized dopamine, both actions being accompanied by an increase in tyrosine hydroxylase activity and dopamine turnover which in turn reduces p-tyramine but produces no change or an increase in m-tyramine.6 The effects of nomifensine were observed after the administration of a relatively high dose (20 mg/kg), that was lethal to some mice (about 20%, at 2 h), and more likely to posses unspecific actions.

Electrolytic lesions of the median and dorsal raphé nuclei resulted in statistically significant reductions in rat hypothalamic noradrenaline which were observed 1 or 2 days after lesioning, while no changes were observed 7 or 14 days after lesioning. The short term (1-2 days) raphé nuclei lesions produced no changes in hypothalamic 5-hydroxytryptamine or a small reduction in 5-hydroxyindole acetic acid while the expected marked reductions were observed after 7 days. The reduction in hypothalamic noradrenaline observed after short term raphé nuclei lesions suggests the existence of a positive feedback loop between 5-hydroxytryptamine neurons and noradrenaline terminals in the hypothalamus.

Tryptamine levels have been determined in mouse brain regions and spinal cord and in rat spinal cord. They were; caudate nucleus 2.5 ng X g-1, hypothalamus less than 0.5 ng X g-1, hippocampus less than 0.7 ng X g-1, olfactory bulb less than 0.7 ng X g-1, olfactory tubercles less than 0.6 ng X g-1, brain stem less than 0.4 ng X g-1, cerebellum less than 1.0 ng X g-1, and the "rest" 0.9 ng X g-1. The mouse whole brain was found to have 0.5 ng X g-1, the mouse spinal cord 0.3 ng X g-1, and the rat spinal cord 0.3 ng X g-1. These concentrations increased rapidly to 22.8 ng X g-1, 14.2 ng X g-1, and 6.6 ng X g-1 respectively at 1 hr after 200 mg X kg-1 pargyline. The turnover rates and half lives of tryptamine in the mouse brain and spinal cord and rat spinal cord were estimated to be 0.14 nmol X g-1 X h-1 and 0.9 min; 0.054 nmol X g-1 X h-1 and 1.5 min and 0.04 nmol X g-1 X h-1 and 1.6 min respectively. The aromatic L-aminoacid decarboxylase inhibitors NSD 1034 and NSD 1055 reduced synthesis of tryptamine in controls and pargyline pretreated animals. Tryptophan increased the concentrations of mouse striatal tryptamine and 5-hydroxytryptamine and brain stem 5-hydroxyindole acetic acid. p-Chlorophenylalanine reduced formation of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid but did not change that of tryptamine.

Following electric stimulation of the substantia nigra for 1 h there was a substantial increase in dopamine (DA) turnover in the rat caudate nucleus evidenced by an increase in its acid metabolite homovanillic acid (HVA). Concurrently there was an increase in striatal m-tyramine (mTA) and a substantial decrease in p-tyramine (pTA). Lesioning the substantia nigra to decrease impulse flow resulted in a buildup of striatal DA and mTA, but again a decrease in pTA. Following pretreatment with a tyrosine hydroxylase inhibitor, the effects of stimulation of the nigra on mTA were reversed, there being a significant decrease in this amine. The decrease of pTA in response was partially prevented by tyrosine hydroxylase inhibition. The effects of stimulation or substantia nigra lesions on pTA levels were reversed, however, by tyrosine hydroxylase inhibition, a significant increase in this amine being recorded. mTA and DA levels were largely unaffected by a combination of lesion and tyrosine hydroxylase inhibition. The results provide insight into the possible biosynthetic interrelationships between DA and the tyramine isomers in the rat caudate nucleus.

1 The endogenous concentrations of p- and m-tyramine in the mouse striatum were determined by a mass spectrometric integrated ion current technique and concentrations were 21.3 and 6.1 ng/g, respectively.2 The present results further confirm that the administration of antipsychotic drugs (chlorpromazine, haloperidol, spiroperidol, alpha-flupenthixol and (+)-butaclamol) reduces p-tyramine concentrations in the mouse striatum. In contrast, striatal m-tyramine showed a tendency to increase, although only in the cases of haloperidol and (+)-butaclamol were the differences statistically significant.3 Administration of antipsychotic drugs to mice pretreated with tranylcypromine or clorgyline produced a significant reduction in striatal p-tyramine when compared with the concentrations obtained in mice given a monoamine oxidase inhibitor. These results suggest that antipsychotic drugs reduce striatal p-tyramine formation. The moderate increases produced by monoamine oxidase inhibitors on striatal m-tyramine were not significantly changed after the administration of an antipsychotic.4 Drugs that reduce dopamine turnover (apomorphine, piribedil, lergotrile, alpha-methyl-p-tyrosine) significantly increased the concentration of striatal p-tyramine. No significant changes were observed in striatal m-tyramine concentrations after apomorphine, piribedil or lergotrile; alpha-methyl-p-tyrosine produced a reduction in its concentration.5 Drugs that impair amine storage (reserpine, tetrabenazine, oxypertine) reduced striatal concentrations of p-tyramine. The m-tyramine concentrations were also reduced by reserpine or tetrabenazine.6 It is possible that striatal tyramines act as modulators, or transmitters, and control the activity of dopaminergic neurones.

Administration of phenelzine (100 mg/kg. i.p., 18 hr) increased rat striatal concentrations of pTA, mTA and DA by 30, 6.7 and 1.5 fold, respectively. Lesions of the medial forebrain bundle prevented these increases, permitting the conclusion that the phenelzine-induced amine increases were localized in the synaptic terminals. The release of endogenous pTA, mTA and DA from striatal slices obtained from phenelzine-treated rats was investigated, 50 mM KC1l elicited releases of pTA, mTA and DA which were significantly greater than their respective basal releases. These K+-stimulated releases were antagonized significantly by 15 mM MgCl2, suggesting that they are calcium-dependent in nature. We have concluded, therefore, that mTA and pTA, as well as DA, are released from striatal nerve terminals in vivo. The total amounts of mTA and DA, but not pTA, released in the release experiments were greater than those found in the nonincubated tissue. It appears, therefore, that the biosynthesis of mTA and DA was stimulated during the incubation of the striatal slices.

The administration of carbidopa (5-50 mg/kg), a peripheral L-aromatic aminoacid decarboxylase inhibitor, significantly increased striatal tyramines; maximal effects were observed at 2-4 hr after treatment. Benserazide produced similar effects. The drug, NSD 1034, that inhibits both central and peripheral decarboxylase, produced a dose-dependent reduction in striatal p-tyramine; in contrast, concentrations of m-tyramine were increased by the smaller doses (2-20 mg/kg) and reduced by the larger dose (400 mg/kg). The results support the view that the tyramines are formed within the brain by decarboxylation of their parent aminoacids but by different mechanisms.

This is a report of the concentrations of DA, DOPAC, HVA, 5-HT, and 5-HIAA in the brain of spontaneously diabetic male Wistar rats. These rats showed a marked increase in blood and urine glucose, polydipsia, polyuria, and weight loss that had an onset 11-23 days earlier. Controls were litter mates with no hyperglycemia, glucosuria or weight reduction. The spontaneously diabetic rats showed a significant reduction of DOPAC in the striatum, and DOPAC, HVA, and 5HIAA in the olfactory tubercles (to 69, 61, 62, and 65% of their respective controls). No changes were found in the concentrations of DA or 5-HT. Thus the spontaneously diabetic rats showed a marked reduction in striatal and mesolimbic DA and mesolimbic 5-HT metabolism. This reduction in metabolism could be the consequence of a reduction in the formation of DA and 5-HT.

This report shows the existence of endogenous p-tyramine in the nerve cord and some organs of the lobster. Their concentrations are lower than those of dopamine or 5-hydroxytryptamine. The nerve cord levels of m-tyramine, beta-phenylethylamine and tryptamine are much lower than those of the phenolic or catecholic amines. The finding that the administration of an aromatic-L-amino acid decarboxylase inhibitor leads to a decrease of p-tyramine gives further evidence that this amine is synthesized from p-tyrosine, which is also found in high concentrations in the lobster nerve cord. The widespread distribution of p-tyramine in the nervous system and peripheral tissues of the lobster suggests that this amine may have additional roles rather than functioning only as a precursor of p-octopamine.

1. Bovine coronary and other arteries contain more dopamine (DA) [1400-520 ng g-1] than noradrenaline (NA) [120-500 ng g-1] with high DA/NA ratios (1.8-4.3). Arteries from other species, (pigs, rats, mice or guinea-pigs), contain far less DA (20-60 ng g-1) and have lower DA/NA ratios (0.01-0.06). 2. Bovine arteries also have 3,4-dihydroxyphenylacetic acid (80-290 ng g-1) but not homovanillic acid (less than 20 ng g-1). 3. It remains to be elucidated whether, in the bovine arterial wall, DA is a transmitter or it is associated with chromaffin-like cells.

1 The concentrations of p- and m-tyramine, dopamine, 3,4-dihydroxyphenylacetic acid and homo-vanillic acid were measured in the mouse or rat striatum following the subcutaneous injection of molindone or fluphenazine. The mouse hypothalamic levels of the m- or p-isomers of octopamine were also analysed. 2 Endogenous concentrations of p- and m-tyramine in the mouse striatum and p- and m-octopamine in the mouse hypothalamus were 20.6, 5.7, 9.4 and 1.2 ng/g respectively. The rat striatum concentrations of p- and m-tyramine were 12.8 and 3.8 ng/g. 3 The administration of low doses of molindone (1 to 10 mg/kg) produced a reduction in striatal p-tyramine, an increase in m-tyramine and an increase in dopamine turnover. Similar effects were produced by all doses of fluphenazine (0.1 to 5 mg/kg) employed. These findings are consistent with those observed after blockade of dopamine postsynaptic receptors. 4 With high doses of molindone (100 mg/kg) the effects on both tyramines and on dopamine metabolism were reversed. These results can be interpreted as molindone acting as a partial agonist. 5 The concentrations of hypothalamic p- and m-octopamine were increased by the higher doses of molindone (20 to 100 mg/kg) employed while lower doses produced no significant effects. All doses of fluphenazine reduced hypothalamic p-octopamine. These changes seem to depend on differences in the availability of p-tyramine to be converted into p-octopamine. 6 These results suggest that molindone acts as a blocker or a partial agonist of dopamine receptor sites and fit well with the proposal of a reciprocal relation between dopamine and tyramine. It is not possible yet to ascertain whether tyramine controls dopamine or vice versa or if it is a direct or a more remote relation.