Cerebral artery selective inhibition of protein kinase c-mediated contraction by hns-32, a novel azulene-1-carboxamidine derivative.
The vasorelaxant actions of a novel azulene-1-carboxamidine derivative, HNS-32, were investigated on the tension development evoked by phorbol 12, 13 dibutyrate (PDBu) in cerebral and femoral arteries isolated from the dogs. In basilar artery, HNS-32 inhibited almost completely PDBu-induced contraction in a concentration-dependent manner with potency about 10 times stronger than that of fasudil, a protein kinase inhibitor. In contrast, in femoral artery, HNS-32 failed to suppress the tension development in response to PDBu whereas fasudil inhibited it with a similar potency as in basilar artery. These findings indicate that HNS-32 selectively suppresses cerebral artery contraction mediated via an activation of protein kinase C.
Noguchi
K
K
Pharmacology Laboratory, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan. s15922@ccm.taisho.co.jp
Saitoh
M
M
Nakazawa
T
T
Tanaka
H
H
Tanaka
Y
Y
Shigenobu
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001488:Basilar Artery / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D002536:Cerebral Arteries / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D011725:Pyridines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C108264:HNS 32; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C