Pharmacological characterization of the 5-hydroxytryptamine receptor coupled to adenylyl cyclase stimulation in human brain
| Autor: | C.A. Rizzi, Ettore Giraldo, Riccardo Rodriguez y Baena, Marco Parenti, Paolo Gaetani, Andrea Zocchetti, E. Monferini |
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| Rok vydání: | 1993 |
| Předmět: |
Agonist
Male medicine.medical_specialty Serotonin medicine.drug_class Stimulation Biology In Vitro Techniques General Biochemistry Genetics and Molecular Biology Adenylyl cyclase 5-Methoxytryptamine chemistry.chemical_compound Bridged Bicyclo Compounds Internal medicine medicine Radioligand Humans General Pharmacology Toxicology and Pharmaceutics Receptor ADCY9 General Medicine Middle Aged Receptor antagonist Bridged Bicyclo Compounds Heterocyclic Frontal Lobe Endocrinology chemistry Receptors Serotonin Benzimidazoles Female Signal transduction Adenylyl Cyclases Signal Transduction |
| Zdroj: | Life sciences. 52(9) |
| ISSN: | 0024-3205 |
| Popis: | Recently, a 5-hydroxytryptamine (5-HT) receptor has been described, whose pharmacology was distinct from that of the already known serotonergic receptors, so that it has been called 5-HT 4 . Because the lack of a high affinity radioligand, the identification of this receptor depends entirely on functional pharmacological analysis. Its stimulation leads to an increase in cyclic AMP accumulation in mouse embryo colliculi neurons, in guinea pig hippocampus and in human heart. We studied the effect of two indoleamines, 5-HT and 5-methoxytryptamine (5-MeO-T), and a benzimidazolone derivative, BIMU 8, in stimulating basal adenylyl cyclase activity in human frontal cortex, and characterized the receptor subtype involved. In membranes prepared from this tissue, 5-HT, 5-MeO-T and BIMU 8 dose-dependently stimulated (13–25 %) the basal enzyme activity (220 pmoles cyclic AMP/min/mg protein). 5-MeO-T behaved as a full agonist, BIMU 8 elicited about 60 % of the maximal 5-HT effect. The selective 5-HT 1A agonist 8-OH-DPAT, was devoid of any stimulating activity. ICS 205–930, a low affinity 5-HT 4 receptor antagonist, completely reversed the effect of all three agonists at high concentrations. Therefore, the present data are consistent with the 5-HT-mediated stimulation of adenylyl cyclase in human frontal cortex resulting by the activation of a 5-HT 4 receptor subtype. |
| Databáze: | OpenAIRE |
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