Phorbol dibutyrate contractions in rabbit aorta: calcium dependence and sensitivity to nitrovasodilators and 8-BR-cyclic GMP.
Phorbol esters activate protein kinase C and induce contraction in vascular smooth muscle. The role of Ca and the sensitivity of this response to nitrovasodilators were evaluated in rabbit aortic rings. Phorbol dibutyrate (PDB) (0.01-10 microM) elicited a concentration-dependent contraction of rabbit aortic rings. Responses to PDB in a salt solution (SS) containing 2.54 mM CaCl2 were not significantly different from those in SS containing 0 Ca and 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Contractions to PDB (1 microM) in zero Ca SS were not reduced by depletion of the norepinephrine-sensitive pool of intracellular Ca. The Ca entry blockers verapamil (100 microM) and nifedipine (100 microM) did not affect PDB (1 microM) responses. Nitroprusside (0.1-10 microM) and nitroglycerin (0.1-10 microM) inhibited PDB contractions in both normal SS and Ca-free SS. 8-Br-cyclic GMP (100 microM) also inhibited PDB responses. Effects of PDB on 45Ca fluxes were evaluated in separate experiments. PDB (1 and 10 microM) elicited contraction, but no change in 45Ca uptake or efflux. In contrast KCl (80 mM) and norepinephrine (10 microM) elicited an increase in both influx and efflux, reflecting a rise in cytosolic Ca. The data suggest that PDB-induced contractions in rabbit aorta are independent of extracellular Ca and are not associated with a rise in cytosolic Ca as detected by calcium flux studies.(ABSTRACT TRUNCATED AT 250 WORDS)
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D010703:Phorbol Esters; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride; D014700:Verapamil; D005996:Nitroglycerin; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine