12-Deoxyphorbol 13-isobutyrate contracts isolated rat thoracic arteries.
The vasocontractile effect of 12-deoxyphorbol 13-isobutyrate (DPB), an activator of protein kinase C (PKC), was studied to clarify the mechanism of the vascontractile response elicited by activation of PKC. DPB induced both a sustained increase in intracellular Ca2+ levels and contraction in isolated rat thoracic artery. For a given increase in intracellular Ca2+ levels. DPB induced a greater contraction than high K+ or ionomycin. In Ca(2+)-free media, DPB induced concentration-dependent contraction with a slow rate of rise without causing detectable changes in intracellular Ca2+ levels. The DPB-induced contractions in Ca(2+)-free media were less inhibited by the inhibitors of calmodulin or myosin light chain kinase than ionomycin-induced contractions in normal media were. These results indicate that activation of PKC might increase the Ca2+ sensitivity of contractile elements due to mechanisms not associated with the Ca(2+)-calmodulin pathway.
Nakajima
S
S
Shionogi Research Laboratories, Osaka, Japan.
Kawakami
M
M
Ueda
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013895:Thoracic Arteries / Q000187:drug effects
D010703:Phorbol Esters; C039067:12-deoxyphorbol 13-isobutyrate; D011493:Protein Kinase C; D002118:Calcium