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Enjalbert A, Bourgoin S, Hamon M, Adrien J, Bockaert J.
“Postsynaptic Serotonin-Sensitive Adenylate Cyclase in the Central Nervous System. II. Comparison with Dopamine- and Isoproterenol-Sensitive Adenylate Cyclases in Rat Brain”.
Molec. Pharmacol.. 1978;14(I):11-23.
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Abstract
The development and distribution of the postsynaptic serotonin (5-HT)-isoprenaline (ISO) and dopamine (DA)-sensitive adenylate cyclase (AC) were studied, in rat and guinea pig brain. Methods Adult male, pregnant female and newborn Sprague-Dawley rats and adult male and pregnant female guinea pigs were used. Brain and spinal cord homogenates were prepared. AC activity (ACA) was assayed in the presence of theophylline using a-32P ATP. Electrolytic lesions of B7 and B8 raphe nuclei were performed on the 4th day postpartum. Various 5-HT agonists and antagonists, neuroleptics and 1-ISO (Sigma) were examined for their effect on ACA in newborn rat brain and in the p-adrenergic sensitive enzyme of C6 glioma. Results 5-HT (Merck)-sensitive AC with apparent affinity of 1 mcM 5-HT was present in collicular, hypothalamic and spinal cord homogenates of rat and guinea pig. The distribution of the 5-HT sensitive enzyme in the new-born rat correlated with the serotoninergic innervation of young and adult, rats but not with dopaminergic innervation. The electrolytic lesions did not affect the 5-HT enzyme characteristics, indicating a postsynaptic localization. Stimulation of ACA by 5-HT and 1-ISO strictly additive unlike that of 5-HT and DA (Calbiochem). The 5-HT sensitive enzyme was stimulated by the agonists (LSD; bufotenine, 5-methoxy-N,N-dimethyltryptamine) (Aegis) and inhibited by the antagonists (methiothepin (Roche), methergoline (Farmitalia), cinanserin, cyproheptadine (Merck-USA) and mianserin (Organon) and neuroleptics (thioridazine (Sandoz), fluphenazine, (Squibb), haloperidol, thioproperazine, chlorpromazine (Rhone Poulen), a-flupentixol (Labaz) and doxapine); only the inhibition by merthergoline was competitive. The agonists, antagonists and neuroleptics did not affect the C6 glioma cell AC apart from inhibition by LSD. DA sensitive AC was inhibited competitively by the antagonists and neuroleptics.
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