Control of the release of newly synthetized 3H-5-hydroxytryptamine by nicotinic and muscarinic receptors in rat hypothalamic slices

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Abstract
Summary The effects of various cholinergic agonists and antagonists on the spontaneous release of newly synthetized 3H-5-HT were examined in rat hypothalamic slices. 3H-5-HT was measured in incubating medium at the end of a 30 min incubation carried out with l-3H-tryptophan in the presence of the various durgs tested. ACh (10−5 M) in the presence of eserine (2×10−4 M), and carbachol (10−5 M) stimulated the release of 3H-5-HT. In contrast, oxotremorine (10−5 M) reduced the 3H-amine release. The effect of carbachol was blocked by two nicotinic blockers, mecamylamine (10−6 M) and d-tubocurarine (10−6 M). It was not reduced by the muscarinic antagonists, atropine (10−6 M) and scopolamine (10−6 M). In fact, each of two antagonists added alone to the incubating medium enhanced 3H-5-HT release. The scopolamine (10−6 M) stimulating effect on 3H-5-HT release was suppressed by d-tubocurarine (10−6 M). Finally, the inhibiting effect of oxotremorine on 3H-5-HT release was not prevented by d-tubocurarine (10−6 M) but was in the presence of atropine (10−6 M) or scopolamine (10−6 M). In the concentrations used in the release study, the cholinergic agonists and antagonists had no effect on the total formation of 3H-5-HT and 3H-5-HIAA from l-3H-tryptophan and on the accumulation of l-3H-tryptophan in tissues. In these concentrations, except for eserine, they did not affect the uptake of exogenous 3H-5-HT in hypothalamic synaptosomes (P2 fraction). These results suggest that cholinergic receptors of the muscarinic and nicotinic type are involved in the control of 3H-5-HT release; since the stimulation of the muscarinic and nicotonic cholinergic receptors resulted in an inhibition and an activation of 3H-5-HT release, respectively. As in the case of peripheral noradrenergic and central dopaminergic neurons the cholinergic receptors could be localized on serotoninergic terminals.