Modulation of protein kinase C (PKC)-mediated contraction and the possible role of PKC epsilon in rat mesenteric arteries.
he involvement of protein kinase C (PKC) in isometric tension development of rat mesenteric arteries was investigated. Non-selective inhibition of PKC and selective inhibition of the epsilon isoform were performed using the PKC inhibitor, chelerythrine, and non-viral gene-transfer of a kinase inactive mutant of PKCepsilon (PKCepsilon-KN), respectively. Chelerythrine (2.5 or 5.0 microM) significantly and equally attenuated phenylephrine-induced but not potassium-induced contractions. Higher concentrations of chelerythrine (10 microM) caused the vessels to lose responsiveness to both phenylephrine and potassium chloride. Transfection of blood vessels with epsilon-KN also resulted in significant attenuation of contractile responses to phenylephrine. Potassium chloride-induced responses were not altered in transfected arteries. In a separate group of vessels, the relationship between [Ca2+]i and isometric tension was evaluated. These studies suggested that calcium sensitivity of the contractile apparatus was decreased in vessels when PKC-epsilon activity was compromised. The results of the study suggest that PKC-epsilon can modulate phenylephrine-induced contraction in mesenteric arteries via calcium-independent pathways.
Shirasawa
Yuichi
Y
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota, Grand Forks, North Dakota 58202, USA.
Rutland
Travis J
TJ
Young
Jennifer L
JL
Dean
David A
DA
Joseph
Benoit N
BN
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D018014:Gene Transfer Techniques; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009154:Mutation; D010617:Phenanthridines / Q000494:pharmacology; D010656:Phenylephrine / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051744:Protein Kinase C-epsilon; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D000470:Alkaloids; D053119:Benzophenanthridines; D007527:Isoenzymes; D010617:Phenanthridines; D010656:Phenylephrine; C016299:chelerythrine; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D002118:Calcium