DIFFERENTIAL FUNCTIONAL-ACTIVITY OF 5-HYDROXYTRYPTAMINE RECEPTOR LIGANDS AND BETA-ADRENERGIC-RECEPTOR ANTAGONISTS AT 5-HYDROXYTRYPTAMINE(1B) RECEPTOR-SITES IN CHINESE-HAMSTER LUNG FIBROBLASTS AND OPOSSUM RENALEPITHELIAL-CELLS

Functional activity of 5-hydroxytryptamine (5-HT) receptor ligands and beta adrenergic receptor antagonists was studied at 5-HT1B receptor s ites in Chinese hamster lung (CHL) fibroblasts by measuring two cellul ar 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 inhi bit forskolin-induced cyclic AMP formation and their potency to potent iate bFGF-induced thymidine incorporation in CHL fibroblasts. Potent a gonist activity was measured with -methoxy-3,1,2,3,6-tetrahydro-4-pyid inyl-1H-indole (RU 24,969), 5-carboxamidotryptamine (5-CT), )-tetrahyd ro-4-pyridyl-5-pyrrolo(3,2-b)pyril-5-one (CP 93,129) and 5-HT, whereas sumatriptan displayed weak agonist activity at concentrations differe nt from its binding affinity for 5-HT1B binding sites. In contrast to the observed 5-HT1B receptor-mediated agonist activity in opossum kidn ey cells for metergoline and the beta adrenergic receptor antagonists: cyanopindolol, 4-(3-tert-butyl-amino-2-hydroxypropoxy)-indole-2 carbo nic acid isopropyl ester (SDZ 21,009), isamoltane, (-)-propranolol and (-)-pindolol, antagonist activity at 5-HT1B receptor sites was yielde d in CHL fibroblasts in accordance with the reported observations at r at brain 5-HT1B receptors. Methiothepin was the only compound that ant agonized both the opossum kidney cell and CHL fibroblast 5-HT1B recept or-mediated responses although the antagonist effect was more pronounc ed in CHL fibroblasts. In conclusion, both 5-HT1B receptor cell system s allow to measure different degrees of agonist or antagonist potencie s of compounds and are particularly useful to define agonist, partial agonist or antagonist activity of compounds with affinity for 5-HT1B r eceptors.