The role of tyrosine kinase in Ca²⁺-independent contraction of the ropivacaine on rat aortic smooth muscle.
The tyrosine kinase signaling pathway plays an important role in the mediation of Ca²⁺ independent mechanisms of smooth muscle contraction. Several components of this pathway, including protein kinase C (PKC), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and Rho-kinase are involved in Ca²⁺ independent mechanisms. Whether the tyrosine kinase pathway mediates vasoconstriction induced by the anesthetic ropivacaine remains unclear. The present study was designed to examine the role of tyrosine kinase in ropivacaine-induced, Ca²⁺-independent contraction of rat aortic smooth muscle. The effects of tyrosine kinase inhibitor on ropivacaine-induced contractile response were observed by isometric force measurement. The protein tyrosine phosphorylation, PKC, p44/42 MAPK, and membrane translocation of Rho-kinase were examined by Western blotting. Ropivacaine induced a concentration-dependent contractile response, and showed a number of effects on protein tyrosine phosphorylation. In this study, phosphorylation levels were shown to increase at lower concentrations of ropivacaine, but the levels decline at higher concentrations in rat aortic rings attenuated by the tyrosine kinase inhibitor genistein in a concentration-dependent fashion. Ropivacaine-induced phosphorylation of PKC and p44/42 MAPK and Rho-kinase membrane translocation were also significantly attenuated by genistein in similar decreasing manner as the PKC inhibitor bisindolylmaleimide I (Bis I) and the Rho-kinase inhibitor, Y27632, but to a lesser degree than that by the p44/42 MAPK inhibitor, PD 098059. Our results showed that the ropivacaine-induced, Ca²⁺ independent-mediated contraction of rat aortic smooth muscle is, in part, regulated by tyrosine kinase-catalyzed protein tyrosine phosphorylation.
Department of Anesthesiology, Qilu Hospital, Shandong University,107, Wenhua Xi Road, Jinan 250012, Shandong, People's Republic of China.
Zhen
Z
Lei
Jianbo
J
Wu
Tao
T
Meng
Qiyu
Q
Bo
Xinyu
X
Zhang
Jingya
J
Yu
Jingui
J
Yu
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine; D014661:Vasoconstriction / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000378:metabolism
D000577:Amides; D000077212:Ropivacaine; D011505:Protein-Tyrosine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium