title: N-(4-Trifluoromethylphenyl)amide group of the synthetic histamine receptor agonist inhibits nicotinic acetylcholine receptor-mediated catecholamine secretion.
abstract: The therapeutic targeting of nicotinic receptors requires the identification of drugs that selectively activate or inhibit a limited range of nicotine acetylcholine receptors (nAChRs). In this study, we identified N-(4-trifluoromethylphenyl)amide group of the synthetic histamine receptor ligands, histamine-trifluoromethyltoluide, that act as potent inhibitors of nAChRs in bovine adrenal chromaffin cells. Catecholamine secretion induced by the nAChRs agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), was significantly inhibited by histamine-trifluoromethyltoluide. Real time carbon-fiber amperometry confirmed the ability of histamine-trifluoromethyltoluide to inhibit DMPP-induced exocytosis in single chromaffin cells. We also found that histamine-trifluoromethyltoluide inhibited DMPP-induced [Ca(2+)](i) and [Na(+)](i) increases, as well as DMPP-induced inward currents in the absence of extracellular calcium. Histamine-trifluoromethyltoluide had no effect on [(3)H]nicotine binding or on calcium increases induced by high K(+), bradykinin, veratridine, histamine, and benzoylbenzoyl ATP. Among the synthetic histamine receptor ligands, clobenpropit exhibited similarity. In addition, 4'-nitroacetanilide also significantly attenuated nAChR-mediated catecholamine secretion. In conclusion, the N-(4-trifluoromethylphenyl)amide group of the histamine-trifluoromethyltoluide might be the critical moiety in the inhibition of nAChR-mediated CA secretion.
authors.affiliation: Division of Molecular and Life Science, SBD-NCRC, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Dong-Chan
authors.initials: DC
authors.lastname: Kim
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Jun
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Hur
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Bo-Hwa
authors.initials: BH
authors.lastname: Choi
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D017442:Histamine Agonists / Q000737:chemistry*; D008345:Manganese / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000378:metabolism
chemical_list: D001549:Benzamides; D002395:Catecholamines; D017442:Histamine Agonists; D011978:Receptors, Nicotinic; D008345:Manganese; D012964:Sodium; D002118:Calcium