The role of protein kinase C in thromboxane A2-induced pulmonary artery vasoconstriction.
In order to determine if protein kinase C (PKC) plays a significant role in the stimulant action of thromboxane A2 (TxA2) on pulmonary vascular smooth muscle, TxA(2)-induced contractile responses were measured following inhibition of PKC. Rabbits were sacrificed and segments of the main trunk of the pulmonary artery were removed and placed within a temperature-controlled (37 degrees C) organ bath. Contractile responses that were evoked by a TxA2 mimetic (U46,619, 0.5 microM) decreased by 27 and 35% following treatment with the PKC inhibitors, calphostin C (2 microM) and staurosporine (200 nM), respectively. These results account for the effect of the vehicle, DMSO, which was also found to have a concentration-dependent inhibitory effect on the U46,619-induced contractions. The effects of DMSO alone was subsequently subtracted from the previously measured responses to PKC inhibitors that were dissolved in DMSO to obtain effects attributable to the PKC inhibitor alone. It can therefore be concluded that inhibition of PKC results in partial attenuation of U46,619-induced responses supporting the hypothesis that activation of PKC plays a partial role in TxA2-induced contraction of pulmonary arterial smooth muscle.
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
Y M
YM
Murtha
B M
BM
Allen
J A
JA
Orr
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D019311:Staurosporine / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D004121:Dimethyl Sulfoxide