5-HT4 receptor activation induces relaxation and associated cAMP generation in rat esophagus
| Autor: | Dai-Chang Yang, G. W. Gullikson, Chafiq Moummi |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Agonist Serotonin medicine.medical_specialty medicine.drug_class Muscle Relaxation Radioimmunoassay Methysergide 5-HT4 receptor Biology 5-Methoxytryptamine chemistry.chemical_compound Esophagus Internal medicine Cyclic AMP medicine Animals Receptor 5-HT receptor Pharmacology Forskolin Dose-Response Relationship Drug Antagonist Muscle Smooth Rats Inbred Strains musculoskeletal system Rats Renzapride Endocrinology chemistry Receptors Serotonin Serotonin Antagonists medicine.drug |
| Zdroj: | European Journal of Pharmacology. 216:47-52 |
| ISSN: | 0014-2999 |
| Popis: | Changes in mechanical events and intracellular levels of cAMP induced by the activation of the 5-HT4 receptor were investigated in the rat esophagus tunica muscularis mucosae preparation. Serotonin (5-HT) and 5 methoxytryptamine (5-MOT; 5-HT4 agonist) caused concentration-related relaxation responses, while 5-carboxamidotryptamine (5-CT; 5-HT1 agonist), 1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (DOI; 5-HT2 agonist) and 2-methyl-serotonin (2-methyl-5-HT; 5-HT3 agonist) were less active. The prokinetic agents, cisapride and renzapride also induced concentration-dependent relaxation of rat esophagus which was intermediate to 5-HT and 5-MOT in potency. The relaxation was not due to activity at receptors other than the 5-HT4 since methysergide (5-HT1 and 5-HT2 antagonist) and granisetron (5-HT3 antagonist) did not block the relazant response to 5-HT while ICS 205930 (5-HT4 antagonist) antagonized this response (pA2 = 6.45). Serotonin also caused concentration-related increases in tunica muscularis mucosae cAMP with the rank order of efficacy of 5-HT agonists in raising tissue cAMP levels reflecting their relaxant activities (5HT⩾5-MOT>5-CT>DOI = 2-methyl-5-HT = control). Enhancement of cAMP concentrations was also observed following renzapride treatment. This cAMP relaxation response was specific for 5-HT4 receptor actication as demonstrated by the lack of ICS 205930 inhibition of rat esophagus relaxation caused by isoproterenol, 16,16-dimethyl-prostaglandin E2 and forskolin. ICS 205930 (10−5 M) alone, however, significantly decreased tissue cAMP, emphasizing its lack of selectivity as an antagonist for blocking the 5-HT4-mediated rise in cAMP. These data suggest that the activation of the putative 5-HT4 receptor mediates rat esophagus relaxation via generation of cAMP. |
| Databáze: | OpenAIRE |
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