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 [Ca2+]i and [Na+]i increases, as well as DMPP-induced inward currents in the absence of extracellular calcium. Histamine-trifluoromethyltoluide had no effect on [ 3H]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.
Original language | English (US) |
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Pages (from-to) | 670-682 |
Number of pages | 13 |
Journal | Biochemical Pharmacology |
Volume | 71 |
Issue number | 5 |
DOIs | |
State | Published - Feb 28 2006 |
Externally published | Yes |
Keywords
- Ca influx
- Catecholamine
- Chromaffin cells
- DMPP
- Histamine-trifluoromethyltoluide
- Nicotinic acetylcholine receptor
ASJC Scopus subject areas
- Biochemistry
- Pharmacology