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The catecholamine content of the carotid body of several mammalian species has been assayed using high performance liquid chromatography coupled to electrochemical detection and radioenzymatic assays. Although there were strain differences in the content of catecholamines in the carotid body of the rat, noradrenaline was equal to or exceeded the dopamine level in this species. No apparent differences were found in carotid bodies of animals killed by cervical dislocation or those dissected from anaesthetized animals. Noradrenaline concentrations were found to be substantially higher than those of dopamine in the cat and guinea-pig carotid body, though dopamine was the predominant amine in the rabbit and ferret. Unilateral superior cervical ganglionectomy or chemical sympathectomy with 6-hydroxydopamine substantially depleted noradrenaline without influencing dopamine in the rat carotid body. A marked selective reduction in noradrenaline was also observed in the rabbit and guinea-pig following ganglionectomy, though similar procedures in the cat failed to alter the levels of either catecholamine in the carotid body. The present data highlights the marked species variation in catecholamine content and the contribution to the latter by sympathetic innervation to this organ. This information will be useful in determining the species specificity regarding the relative roles of dopamine and noradrenaline in the modulation of chemoreceptor afferent discharge.

N-Acetyltyramine, N-acetyldopamine and N-acetyloctopamine were the major products when either L-[3H]tyrosine or [3H]tyramine were incubated with thoracic ganglia of the desert locust, Schistocerca gregaria. No label was incorporated into L-DOPA under these conditions, although 2-3% of the radioactivity could be recovered in dopamine and octopamine. Addition of the aromatic amino acid decarboxylase inhibitor, 3-hydroxybenzylhydrazine (NSD 1015), prevented the formation of N-acetylcompounds from L-[3H]tyrosine, without resulting in an accumulation of label in L-DOPA. In contrast, incubation of samples of haemolymph with L-[3H]tyrosine resulted in the recovery of 7% of label in L-DOPA, which was increased to 17% in the presence of NSD 1015. These results provide evidence that the initial step in the synthesis of dopamine and octopamine by S. gregaria nervous tissue is the conversion of L-tyrosine to tyramine, which is subsequently metabolised to N-acetyltyramine, N-acetyldopamine or N-acetyloctopamine.

An increase in specific dopamine D2 receptor binding sites was observed in membranes prepared from the carotid bodies of rabbits treated for 8 weeks and then withdrawn for 4-9 days from the D2 antagonist domperidone (2-5 mg/kg per day). Recordings of chemoreceptor afferent discharge from the carotid body also revealed that this change in receptor density was accompanied by an increased sensitivity to the chemodepressant effects of exogenous dopamine. The chemoreceptor responsiveness of the carotid body to hypoxia is blunted in rabbits treated chronically with domperidone, but this can be restored to normal by an acute dose of the D2 antagonist. These experiments provide evidence that is compatible with a chemo-inhibitory role for endogenous dopamine in the rabbit's carotid body. Furthermore, these results suggest that the carotid body provides a useful model for the functional studies of dopamine D2 receptors.

1. The effects of the dihydropyridine calcium channel blocker nifedipine and the activator Bay K 8644 were investigated in different behavioural tests involving dopaminergic systems. These were the discriminative stimulus induced by amphetamine, rotational behaviour in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions and apomorphine-induced yawning in rats. 2. The yawning induced by apomorphine (40 micrograms kg-1 s.c.) was significantly potentiated by nifedipine (5-10 mgkg-1 i.p.). Bay K 8644 (0.05-0.5 mgkg-1 i.p.) dose-dependently inhibited yawning induced by apomorphine (80 micrograms kg-1 s.c.) and, at 0.4 mgkg-1, inhibited the nifedipine potentiation of apomorphine-induced yawning. In contrast to their effects on apomorphine-induced yawning, nifedipine and Bay K 8644 had no effect on apomorphine-induced penile erection. 3. Bay K 8644 (0.06-0.5 mgkg-1 i.p.) and nifedipine (5-20 mgkg-1 i.p.) had no dose-related effect on the discrimination performance of rats trained to discriminate amphetamine from saline. However, nifedipine dose-dependently reduced the response rate of amphetamine-treated rats. Bay K 8644 had no effect on this measure except at high doses that also caused disruption. 4. Neither nifedipine (5-10 mgkg-1 i.p.) nor Bay K 8644 (0.06-0.5 mgkg-1 i.p.) affected the turning behaviour induced by amphetamine (1 mgkg-1 i.p.) in rats with unilateral 6-OHDA lesion of the medial forebrain bundle, and did not induce turning themselves. 5. As the dihydropyridine compounds affected apomorphine-induced yawning but not penile erection, and did not affect amphetamine-induced rotation or drug discrimination, it seems unlikely that they are affecting dopamine release in vivo.

Dopamine levels in rat carotid bodies and the effects of intravenous dopamine injections on respiration in adult rats anaesthetized with pentobarbitone have been studied in animals which were treated with capsaicin neonatally. Levels of dopamine were five fold higher in the carotid bodies of capsaicin-treated rats as compared with vehicle-treated controls, but there was no significant difference between capsaicin-treated and vehicle-treated rats in their ID50 values for dopamine-induced respiratory depression. Domperidone, a dopamine D2-receptor antagonist, substantially reduced the respiratory depression caused by dopamine, both in capsaicin-treated and in control animals, suggesting that a D2-receptor was involved in the response. Cutting the carotid sinus nerves greatly reduced the ventilatory-depressant effect of dopamine, showing that sensory receptors, most probably arterial chemoreceptors, were responsible for most of the response. Substantially less reflex hyperventilation was evoked in capsaicin-treated rats by the peripheral chemoreceptor stimulants hypoxia and sodium cyanide, in comparison with the controls, and domperidone did not increase the responsiveness. About 80% of the reflex ventilatory change originated from carotid body chemoreceptors. The hypoventilation caused by breathing 100% O2 was not significantly different in capsaicin-treated rats when compared with controls. Domperidone substantially reduced this response in capsaicin-treated rats, but not in vehicle-treated animals. Dopamine-induced respiratory depression in capsaicin-treated rats was slightly enhanced, rather than reduced, by oxygen breathing; domperidone remained an effective antagonist of dopamine-induced ventilatory depression. Most of the reduction in respiration caused by dopamine in rats anaesthetized with pentobarbitone can be attributed to actions on a dopamine D2-receptor located in the carotid body. However, despite the increased levels of dopamine found in the carotid bodies, the reduced peripheral chemosensitivity observed in anaesthetized capsaicin-treated rats does not appear to result from a change in sensitivity to dopamine.