Differential functional activity of 5-hydroxytryptamine receptor ligands and beta adrenergic receptor antagonists at 5-hydroxytryptamine1B receptor sites in Chinese hamster lung fibroblasts and opossum renal epithelial cells.
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)
Pauwels
P J
PJ
Laboratory of Cellular Neurobiology, Centre de Recherche Pierre Fabre, Castres, France.
Palmier
C
C
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000166:cytology / Q000378:metabolism; D009893:Opossums; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D008024:Ligands; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D000242:Cyclic AMP; D013936:Thymidine