Inhibitory effects of forskolin on vascular smooth muscle of rabbit aorta.
Effects of forskolin on the contractions in rabbit aorta were examined. The sustained contraction induced by 10(-6) M norepinephrine was inhibited by 10(-8)-10(-5) M forskolin in a concentration-dependent manner. In the high K+-depolarized and verapamil-treated aorta, the norepinephrine-induced sustained contraction was similarly inhibited by forskolin. However, forskolin showed only a slight inhibitory effect on the sustained contraction induced by 65.4 mM KCl. Forskolin inhibited the increase in Ca2+ influx due to norepinephrine, but not that due to high K+. In a Ca2+-free solution, 10(-6) M norepinephrine induced a transient contraction which is due to Ca2+ release from the store site. This contraction was inhibited by 3 X 10(-7)-10(-5) M forskolin. However, caffeine-induced transient contraction was not inhibited by 10(-5) M forskolin. 45Ca2+ in a cellular site was released by 10(-6) M norepinephrine or 10 mM caffeine. Forskolin inhibited the Ca2+ release induced by norepinephrine, but not that by caffeine. Forskolin increased the tissue cAMP content in resting, 10(-6) M norepinephrine-treated or 65.4 mM K+-treated aorta. It is concluded that forskolin inhibits the norepinephrine-induced sustained contraction by relatively selectively inhibiting the receptor-linked Ca2+ channel, and it inhibits the norepinephrine-induced transient contraction by inhibiting Ca2+ release from the cellular store.
Abe
A
A
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Karaki
H
H
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits
D002132:Calcium Radioisotopes; D005576:Colforsin; D002110:Caffeine; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine