20-Hydroxyeicosatetraenoic acid potentiates stretch-induced contraction of canine basilar artery via PKC alpha-mediated inhibition of KCa channel.
1. The present study was undertaken to elucidate whether PKCalpha plays a role in the mechanism of the stretch-induced contraction potentiated by 20-hydroxyeicosatetraenoic acid (20-HETE). The effects of 20-HETE on the canine basilar artery were compared with those of iberiotoxin, a blocker of large conductance Ca(2+)-activated K(+) channels (K(Ca) channels), as this blocker was shown earlier to sensitize these arteries to mechanical stretch. 2. Slow stretch at rates of 0.1 to 3 mm s(-1) did not produce any contraction in normal physiological solution. 3. In the presence of 20-HETE, the slow stretch could produce contraction, which was inhibited by nicardipine, a 1,4-dihydropyridine Ca(2+) channel blocker, and gadolinium, a blocker of stretch-activated cation channels. 4. 20-HETE inhibited whole-cell K(+) current and depolarized the membrane by approximately 10 mV. These effects of 20-HETE were similar to those of iberiotoxin. 5. Calphostin C, an inhibitor of protein kinase C (PKC), inhibited the action of 20-HETE, but not that of iberiotoxin. 6. In response to 20-HETE PKCalpha isoform was translocated from the cytosol to the membrane fraction, which translocation was inhibited by calphostin C. 7. These results suggest that 20-HETE induced sensitization of the canine basilar artery to stretch was caused by PKCalpha-mediated inhibition of K(Ca) channel activity.
Obara
Kazuo
K
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Koide
Masayo
M
Nakayama
Koichi
K
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D051571:Protein Kinase C-alpha; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D006893:Hydroxyeicosatetraenoic Acids; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha