Role of protein kinase C in constrictor responses of the rat basilar artery in vivo.
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.
Murray
M A
MA
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, IA.
Faraci
F M
FM
Heistad
D D
DD
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001488:Basilar Artery / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000502:physiology; D004873:Ergolines / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013110:Sphingosine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D004873:Ergolines; D007546:Isoquinolines; D010879:Piperazines; D012702:Serotonin Antagonists; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015237:Dinoprost; D011493:Protein Kinase C; C032663:LY 53857; D013110:Sphingosine