title: The human and dog 5-HT1D receptors can both activate and inhibit adenylate cyclase in transfected cells.
abstract: The cloned human serotonin 1D (5-HT1D) receptor has been shown to inhibit adenylate cyclase while the corresponding cloned dog receptor has been characterized by its enhancement of cAMP accumulation. To resolve this apparent discrepancy, the human 5-HT1D receptor has been cloned and expressed in Chinese hamster ovary (CHO) cells and the corresponding dog receptor expressed in mutant Y1 adrenal (Y1 Kin-8) cells. It is shown that both receptors when activated by sumatriptan depress forskolin induced adenosine 3'5'-cyclic monophosphate (cAMP) accumulation by a pertussis toxin sensitive mechanism, presumably involving Gi (the adenylate cyclase inhibitory GTP transducing protein). In the absence of forskolin, the dog receptor enhances cAMP accumulation, thus activating Gs (the adenylate cyclase stimulatory GTP transducing protein). When its overriding action on Gi is blocked by pertussis toxin pretreatment, the human receptor also enhances cAMP accumulation. Thus both 5-HT1D receptors activate markedly Gi and to a lesser extent Gs and can exert opposite effects on the same effector system, adenylate cyclase.
authors.affiliation: Institute of Interdisciplinary Research (IRIBHN), University of Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Van Sande
authors.forename: A
authors.initials: A
authors.lastname: Allgeier
authors.forename: C
authors.initials: C
authors.lastname: Massart
authors.forename: A
authors.initials: A
authors.lastname: Czernilofsky
authors.forename: G
authors.initials: G
authors.lastname: Vassart
authors.forename: J E
authors.initials: JE
authors.lastname: Dumont
authors.forename: C
authors.initials: C
authors.lastname: Maenhaut
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004789:Enzyme Activation; D006801:Humans; D008969:Molecular Sequence Data; D037342:Pertussis Toxin; D011506:Proteins / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D011506:Proteins; D011985:Receptors, Serotonin; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018170:Sumatriptan; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases