Phorbol ester (PMA)-induced biphasic contraction of the rat aorta and effects of sodium nitroprusside and forskolin on the contraction.
Effects of sodium nitroprusside (SNP) and forskolin on the contractile responses of aortic strips to phorbol 12-myristate 13-acetate (PMA) were investigated in the present study. PMA produced biphasic contraction in the rat aorta, i.e. sustained, slowly developing contraction followed by phasic contraction superimposed on the sustained contraction. Both sustained contraction and phasic response were completely abolished by treatment with staurosporine. Phasic contraction was completely inhibited by nicardipine or removal of external Ca2+, whereas sustained contraction was not affected by nicardipine. Both SNP and forskolin inhibited sustained contraction. Ca(2+)-induced contraction of the aorta which had been treated with PMA in Ca(2+)-free medium was completely inhibited by nicardipine and was partially inhibited by forskolin, but SNP had no effect on the Ca(2+)-contracture. These results suggest that 1) PMA contacts the rat aorta through stimulation of protein kinase C and activation of voltage-dependent Ca2+ channels; 2) there may be great differences in the effects of cyclic GMP and cyclic AMP on the protein kinase C-induced sustained and phasic contractions.
Suenaga
H
H
Department of Pharmacology, Upjohn Research Laboratories, Ibaraki, Japan.
Kamata
K
K
Kasuya
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology*; D004347:Drug Interactions; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; 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 / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015220:Calcium Channels; D009599:Nitroprusside; D005576:Colforsin; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium