Contractile and relaxant effects of tetrapentylammonium ions in rat isolated mesenteric artery
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AbstractBoth contractile and relaxant responses to tetrapentylammonium ions (TPA(+)) were studied in rat isolated mesenteric artery. TPA(+) (5-10 mu mol/l) caused a sustained increase of muscle tension. The contractile effect of TPA(+) (10 mu mol/l) was dependent upon the presence of extracellular Ca2+ but independent of the presence of endothelium. TPA(+) (10-50 mu mol/l) induced biphasic contraction, and the amplitude of peak and sustained tension decreased with increasing TPA(+) concentration. TPA(+) (100-300 mu mol/l) only produced monophasic contraction. TPA(+) (50 mu mol/l) abolished the transient contraction induced by caffeine (10 mmol/l) or phenylephrine (1 mu mol/l) in the absence of extracellular Ca2+. Nifedipine and verapamil concentration-dependently reduced the TPA(+)-induced contraction with respective IC50 values of 1.34 +/- 0.24 and 9.46 +/- 1.36 nmol/l, these values were similar to 1.35 +/- 0.21 and 16.07 +/- 1.71 nmol/l, respectively, for the inhibitory effects of nifedipine and verapamil on the high K+ (60 mmol/l)-induced contraction. TPA(+) (>10 mu mol/l) concentration-dependently reduced the phenylephrine (1 mu mol/l)-, U46619 (30 nmol/l)-, endothelin I (10 nmol/l)- and high K+ (60 mmol/l)-induced sustained tension with respective IC50 values of 53.7 +/- 9.5, 31.9 +/- 5.3, 30.9 +/- 3.4 and 20.9 +/- 2.8 mu mol/l. The present results indicate that TPA(+) at low concentrations could contract the arterial smooth muscle probably through promoting Ca2+ influx. At higher concentrations (>20 mu mol/l), TPA(+) relaxes arterial smooth muscle probably through inhibition of both nifedipine-sensitive Ca+ channels and internal Ca2+ release. TPA(+), unlike other quaternary ammonium ions, could therefore act at multiple sites in arterial smooth muscle.
All Author(s) ListKwok KH, Chan NWK, Lau CW, Huang Y
Journal namePharmacology
Volume Number57
Issue Number4
Pages188 - 195
LanguagesEnglish-United Kingdom
KeywordsCa2+ channels; contraction; K+ channels; mesenteric artery (rat); relaxation; smooth muscle; tetrapentylammonium
Web of Science Subject CategoriesPharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

Last updated on 2020-10-07 at 03:57