Role of Ca2+-sensitive protein kinase C in phenylephrine enhancement of Ca2+ sensitivity in rat tail artery

We investigated the role of protein kinase C (PKC) isoforms on changes in s ensitivity of contractile mechanisms to intracellular Ca2+ (force /[Ca2+](i )) by phenylephrine (0.1-100 muM) in rat tail arterial helical strips using simultaneous measurements of force and [Ca2+](i). Force/[Ca2+](n) induced by phenylephrine was greater than that induced by 80 MM K+. Force/[Ca2+](i) induced by phenylephrine in physiologic saline solution or low Ca2+ soluti on was dependent on the agonist concentration. Removal of Ca2+ completely a bolished the phenylephrine-induced contraction. The PKC inhibitors staurosp orine and calphostin C inhibited the increase in force/[Ca2+](i) induced by phenylephrine to a much greater extent than that induced by 80 mM K+. LY37 9196, a specific PKC beta inhibitor, did not inhibit the increase of calciu m sensitivity due to phenylephrine. The classic PKC isoforms, alpha, betaI, and II not gamma were demonstrated in the artery by immunohistochemistry. These results suggest that in rat tail arterial smooth muscle, PKC alpha, a nd not beta or gamma, mediates the increase of changes in sensitivity of co ntractile mechanisms to intracellular Ca2+ to high dose of alpha (1) recept or stimulation (phenylephrine 100 muM) on nonphysiologic conditions.