Contractile and relaxant effects of tetrapentylammonium ions in rat isolated mesenteric artery.
Both contractile and relaxant responses to tetrapentylammonium ions (TPA+) were studied in rat isolated mesenteric artery. TPA+ (5-10 micromol/l) caused a sustained increase of muscle tension. The contractile effect of TPA+ (10 micromol/l) was dependent upon the presence of extracellular Ca2+ but independent of the presence of endothelium. TPA+ (10-50 micromol/l) induced biphasic contraction, and the amplitude of peak and sustained tension decreased with increasing TPA+ concentration. TPA+ (100-300 micromol/l) only produced monophasic contraction. TPA+ (50 micromol/l) abolished the transient contraction induced by caffeine (10 mmol/l) or phenylephrine (1 micromol/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 micromol/l) concentration-dependently reduced the phenylephrine (1 micromol/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 micromol/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 micromol/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.
Kwok
K H
KH
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Chan
N W
NW
Lau
C W
CW
Huang
Y
Y
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D019332:Endothelin-1; D000644:Quaternary Ammonium Compounds; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C027435:tetrapentylammonium; D014700:Verapamil; D009543:Nifedipine; D011188:Potassium