title: 5-Hydroxytryptamine 5-HT1D receptors mediating inhibition of cyclic AMP accumulation in Madin-Darby canine kidney (MDCK) cells.
abstract: 5-Hydroxytryptamine 5-HT1B/5-HT1D receptors are members of the same receptor subfamily, but display a different pharmacology (Hartig et al. (1992) Trends Pharmacol Sci 13: 152-159). Whereas several cell lines have been reported to contain 5-HT1B receptors, none has been described, however, that endogenously expresses well-characterized 5-HT1D receptors. The present study deals with the identification of 5-HT1D receptors inhibiting cyclic AMP accumulation in Madin-Darby canine kidney (MDCK) cells. 5-HT (1 nM-10 microM) induced a concentration-dependent inhibition of the cyclic AMP accumulation stimulated by prostaglandin E1 (1 microM) in MDCK cells. The maximal effect of 5-HT averaged 50% inhibition and was abolished after a pre-treatment of the cells with pertussis toxin. Other agonists mimicked the effects of 5-HT, with the following rank order of potency (pEC50 +/- SEM, n > or = 3): 5-carboxamidotryptamine (8.36 +/- 0.48) > PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine. 7.89 +/- 0.23) > 5-HT (7.35 +/- 0.05) > sumatriptan (6.65 +/- 0.27). PAPP behaved as a partial agonist. 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) was less potent, its maximal effect being not reached at 0.1 mM. Methiothepin. GR127935, (-)propranolol, rauwolscine and ketanserin were all devoid of intrinsic activity (up to 10 microM or 0.1 mM). Methiothepin (10 nM. 0.1 microM and 1 microM) antagonized 5-HT effect (pA2 8.57 +/- 0.44. Schild slope 1.17 +/- 0.21, n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Sandoz Pharma Ltd, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Schoeffter
authors.forename: I
authors.initials: I
authors.lastname: Bobirnac
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects*; D008719:Methiothepin / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D037342:Pertussis Toxin; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D018170:Sumatriptan / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D010069:Oxadiazoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D010566:Virulence Factors, Bordetella; C090701:GR 127935; D015016:Yohimbine; D012701:Serotonin; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C044643:LY 165163; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D007650:Ketanserin; D011433:Propranolol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000527:Alprostadil