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Postsynaptic α1-adrenoceptor mechanisms in vasa deferentia isolated from 3, 6, 18 and 40 week-old rats were studied by analysis of the concentration-response curve of noradrenaline and the Scatchard plot of specific binding of [3H]prazosin to microsomal fractions. The maximum tension developed by noradrenaline also increased with age from 3 to 18 weeks. The efficacy of noradrenaline and capacity of the maximum binding sites of [3H)prazosin increased with increasing age, while the dissociation constants of noradrenaline (KA) and prazosin (Kd) were not changed with age. The increase of the maximum tension was proportional to the increase in efficacy. The increase of efficacy for noradrenaline in the vasa deferentia from rats of different ages is due to the increase in the total concentration of postsynaptic α1-adrenoceptors.

We have characterized muscarinic cholinergic receptor sites and interaction of various modulators of intracellular Ca mobilization, such as 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8), ryanodine, procaine and related drugs with the receptor sites, using a binding assay method with [3H]quinuclidinyl benzilate [( 3H]QNB) in guinea pig tenia cecum membrane fraction. [3H]QNB bound to a single population of sites, and the binding profile of pirenzepine suggest that the receptor sites are probably the M2 type. All the test drugs examined except for ryanodine displaced the [3H]QNB binding, and the slope factors were not different from unity. Affinities of these drugs were comparable to the concentrations usually used to modulate intracellular Ca mobilization. A Scatchard plot of [3H]QNB binding in the presence of TMB-8 or procaine showed that the apparent dissociation constant for [3H]QNB was increased without change in maximum binding. Neither TMB-8 nor procaine had any effect on the rate of dissociation of [3H]QNB from the steady-state complex. These results suggest that TMB-8 and procaine, and possibly other drugs, may interact directly with the muscarinic cholinergic M2 receptor sites in a competitive manner. In contrast, ryanodine had no effect on the [3H]QNB binding up to at least 100 microM. No interaction of ryanodine with M2 receptor sites lends a further support that the drug could be a useful probe for studying intracellular Ca mobilization.

This study investigates the interactive effects of Ca antagonists and responses to serotonin (5-HT) in isolated rabbit aorta and basilar artery. Isolated strips of rabbit aorta and of basilar artery were studied in organ baths containing 20 ml of Krebs-buffer solution. D 600 or diltiazem caused parallel rightward shifts of concentration-response curves for 5-HT in isolated rabbit aorta, but each reduced the 5-HT-induced maximum response in basilar artery. The slope values from Schild plot analyses in aorta were 1.11 +/- 0.05 and 1.22 +/- 0.37 in D 600 and diltiazem, respectively. Dibenamine pretreatment caused reduction of maximum response to 5-HT in both tissues. Such reduction was diminished markedly by the presence of D 600, diltiazem or 5-HT in aorta but not in basilar artery. Also, the antagonistic effects of D 600 and diltiazem were diminished by elevation of bath Ca in basilar artery but not in aorta. These results strongly suggest that the two Ca entry blockers used in this study might compete with 5-HT at 5-HT receptors in rabbit aorta and that the pharmacomechanical property of 5-HT receptors in rabbit aorta might be distinct from that in rabbit basilar artery.

Interactions of several alpha-adrenoceptor agonists and antagonists with their receptors were studied in rabbit and guinea pig iris dilator smooth muscle and rabbit aortic strips using pharmacological procedures.

Isoamyl acetate, n-butyl acetate, n-amyl acetate and n-propyl acetate produced contractions of the isolated ileum of the guinea-pig. These were inhibited by atropine, procaine and by cooling. These acetates and also s-butyl, t-butyl and n-octyl acetate behaved as inhibitors of acetylcholine at 14 ± 1°. The acetylcholine content in the organ bath fluid increased after 60 min incubation of the ileum with isoamyl acetate. The results indicated that the agonistic acetates produced contraction of ileum through the liberation of acetylcholine from the cholinergic nerve-endings. All the acetates behaved as inhibitors of acetylcholine when they combined with the acetylcholine receptor on the muscle.

The effects of papaverine, isoprenaline and N6,2′-O-dibutyryl 3′,5′-cyclic adenosine monophosphate (DiBu.C-AMP) on calcium movements in the taenia from the guinea-pig caecum have been investigated and compared with the effects of phenylephrine. Papaverine and DiBu.C-AMP antagonized the contraction of KCl-depolarized muscle induced by CaCl2and increased 45Ca-efflux from the taenia. Papaverine also significantly depressed 45Ca-uptake by this preparation. These findings suggest that papaverine impairs the availability of calcium to the contractile system and that there may be a correlation between relaxation and increase of 45Ca-efflux. The action of DiBu.C-AMP resembles that of papaverine but its potency is less.