Mechanisms of vasorelaxation induced by N-allylsecoboldine in rat thoracic aorta.
N-Allylsecoboldine was shown to be the most effective of several boldine derivatives that were tested for their vasorelaxing effect on the rat aorta. In KCl (60 mmol/l) medium, Ca2+ (0.03-3 mmol/l)-induced vasoconstriction was inhibited, concentration-dependently, by N-allylsecoboldine. The IC50 for N-allylsecoboldine was calculated to be about 4 mumol/l (for a Ca2+ concentration of 1 mmol/l). The vasorelaxant effect on KCl-induced responses was more pronounced at 60 mmol/l KCl than at 15 mmol/l KCl. Contraction of rat aorta in response to phenylephrine (0.01-100 mumol/l) was concentration-dependently inhibited by N-allylsecoboldine and by verapamil (3-30 mumol/l), while contraction in response to B-HT 920, serotonin or PGF2 alpha was not affected. This relaxing effect of N-allylsecoboldine persisted in endothelium-denuded aorta. In cultured A10 vascular smooth muscle cells, N-allylsecoboldine and verapamil displaced the binding of [3H]-prazosin (Ki values = 0.4 +/- 0.2 and 0.6 +/- 0.2 mumol/l, respectively). The increase of inositol monophosphate caused by phenylephrine in rat aorta was completely suppressed by chloroethylclonidine, but only slightly inhibited by N-allylsecoboldine and by verapamil. Glibenclamide or charybdotoxin did not affect the relaxation induced by N-allylsecoboldine of aortic rings precontracted with phenylephrine. Neither the cGMP nor the cAMP content was changed by N-allylsecoboldine. We conclude that N-allylsecoboldine relaxes the rat aorta by blocking Ca2+ channels and that it also has an antagonistic effect at alpha 1-adrenoceptors.
Yu
S M
SM
Department of Pharmacology, Chang Gung Medical College, National Taiwan University, Taipei.
Lee
S S
SS
Hou
Y S
YS
Teng
C M
CM
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001060:Aporphines / Q000494:pharmacology*; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019806:Cromakalim; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D001060:Aporphines; D001578:Benzopyrans; D002121:Calcium Channel Blockers; C090152:N-allylsecoboldine; D010716:Phosphatidylinositols; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D014700:Verapamil; D000242:Cyclic AMP; D006152:Cyclic GMP; D011188:Potassium; D005905:Glyburide