Role of calcium in the potentiating effect of phorbol ester on KCl-induced vasocontraction.
The mechanism of the potentiating effect of phorbol ester on potassium-induced contraction in rat aorta was investigated. The contractile response to KCl in the medium containing 0.5 mM CaCl2 was significantly increased by pretreatment with 10(-8) M phorbol 12-myristate 13-acetate (PMA), but not with 10(-7) M 4 alpha-phorbol. The dose-response curve to calcium in 30 mM KCl-induced contraction was shifted to the left by PMA pretreatment and the EC50 value (the concentration producing a half maximal response) of calcium was significantly lower in aorta pretreated with PMA than in the control. On the other hand, calcium influx stimulated by 30 mM KCl was not changed by PMA pretreatment. Both the contractile response and the corresponding calcium influx induced by 30 mM KCl were abolished by preincubation with 10(-6) M verapamil for 45 min. These results suggest that activation of protein kinase C potentiates the contractile response to KCl by increasing the sensitivity of the intracellular contractile apparatus for calcium.
Wakabayashi
I
I
Second Department of Internal Medicine, Hyogo College of Medicine, Japan.
Kakishita
E
E
Hatake
K
K
Hishida
S
S
Nagai
K
K
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D011189:Potassium Chloride; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium