Functional activity of 5-hydroxytryptamine (5-HT) receptor ligands and beta adrenergic receptor antagonists was studied at 5-HT1B receptor sites in Chinese hamster lung (CHL) fibroblasts by measuring two cellular responses: inhibition of forskolin-stimulated cyclic AMP formation and potentiation of basic fibroblast growth (BFGF) induced mitogenesis. A good correlation was found between the potency of agonists to inhibit forskolin-induced cyclic AMP formation and their potency to potentiate bFGF-induced thymidine incorporation in CHL fibroblasts. Potent agonist activity was measured with 5-methoxy-3,1,2,3,6-tetrahydro-4-pyidinyl- 1H-indole (RU 24,969), 5-carboxamidotryptamine (5-CT), 3-(1,2,5,6)-tetrahydro-4-pyridyl-5-pyrrolo(3,2-b)pyril-5-one (CP 93,129) and 5-HT, whereas sumatriptan displayed weak agonist activity at concentrations different from its binding affinity for 5-HT1B binding sites. In contrast to the observed 5-HT1B receptor-mediated agonist activity in opossum kidney cells for metergoline and the beta adrenergic receptor antagonists: cyanopindolol, 4-(3-tert-butyl-amino-2-hydroxypropoxy)-indole-2 carbonic acid isopropyl ester (SDZ 21,009), isamoltane, (-)-propranolol and (-)-pindolol, antagonist activity at 5-HT1B receptor sites was yielded in CHL fibroblasts in accordance with the reported observations at rat brain 5-HT1B receptors. Methiothepin was the only compound that antagonized both the opossum kidney cell and CHL fibroblast 5-HT1B receptor-mediated responses although the antagonist effect was more pronounced in CHL fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
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