Intracellular calcium levels in phorbol ester-induced contractions of vascular muscle.
Intracellular calcium concentration ([Ca2+]i) was measured with aequorin in ferret and rat aortic strips contracted with phorbol esters. In ferret aorta, 12-deoxyphorbol 13-isobutyrate 20-acetate (DPBA, 1 microM) induced contractions without significantly increasing [Ca2+]i, whereas 21 mM K+ induced smaller contractions with a significant rise in [Ca2+]i. Ca2+-free 2.5 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA)-physiological saline solution (PSS) had no effect on DPBA-induced tension, whereas it abolished contractions induced by 66 mM K+. The alpha 1-adrenergic agonist phenylephrine (10(-5) M) induced less than 10% of the tension with no initial [Ca2+]i spike under Ca-free conditions. In rat aorta, both phorbol 12-myristate 13-acetate (PMA, 2 microM) and DPBA (1 microM) induced contractions without increasing [Ca2+]i; Ca2+-free EGTA-PSS or the addition of the calcium channel blocker gallopamil (D600, 1 microM), however, abolished greater than 50% of the tension induced by either phorbol ester with a decrease in [Ca2+]i. These results are consistent with the idea that 1) resting [Ca2+]i is both sufficient and required to support phorbol ester-induced contractions in two vascular smooth muscles, suggesting an increased sensitivity of the contractile apparatus for Ca2+, and 2) there are differences in the mechanisms by which phorbol esters and alpha 1-agonists may activate vascular smooth muscle.
Cardiovascular Division, Charles A. Dana Research Institute, Boston, Massachusetts.
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D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D005289:Ferrets; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010703:Phorbol Esters; D010656:Phenylephrine; C047907:12-deoxyphorbol-13-isobutyrate-20-acetate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium