Role of protein kinase C in constrictor responses of the rat basilar artery in vivo

Abstract

1. The goal of this study was to determine the effects of activation and inhibition of protein kinase C on the rat basilar artery in vivo. 2. The diameter of the basilar artery was measured through a craniotomy in rats anaesthetized with pentobarbitone sodium (50 mg kg-1, I.P., supplemented with 20 mg kg-1 h-1). Diameters were measured under control conditions and during topical application of various agonists, both alone and in the presence of antagonists. 3. Serotonin (5-HT) produced concentration-related constriction of the basilar artery (baseline diameter = 234 +/- 9 microns, mean +/- S.E.M.), which was inhibited by the 5-HT2 receptor antagonist LY53857. 4. Sphingosine (10(-6) M), a protein kinase C inhibitor which binds to the regulatory site of protein kinase C, inhibited the response to 10(-8) M-serotonin (-19 +/- 2% before vs. -3 +/- 2% during sphingosine, P less than 0.05). In contrast, constrictor responses to prostaglandin F2 alpha to (PGF2 alpha; 10(-6) M) were not inhibited by sphingosine (-16 +/- 2% before vs. -18 +/- 2% during sphingosine, P greater than 0.05). 5. H-7 (10(-9) M), another protein kinase C inhibitor, which binds to the catalytic site of protein kinase C, also inhibited constriction of the basilar artery in response to serotonin, but not prostaglandin F2 alpha. 6. Phorbol 12,13-dibutyrate (PDBu, 10(-8) M), which activates protein kinase C, produced slowly developing constriction of the basilar artery. PDBu-induced vasoconstriction (-33 +/- 2%) was attenuated by sphingosine (-11 +/- 4% during sphingosine, P less than 0.05) and H-7 (-1.5 +/- 5% during H-7, P less than 0.05). 7. In summary, activation of protein kinase C appears to mediate vasoconstrictor responses of the basilar artery to serotonin, but not PGF2 alpha.