We studied 40 children younger than 4 yr having elective abdominal surgery under general anaesthesia supplemented with either systemic opioids or extradural bupivacaine. Venous blood samples were obtained before tracheal intubation to measure baseline concentrations of adrenaline, noradrenaline, glucose, ACTH and cortisol. Additional samples were obtained 45 min after the start of surgery, at the end of surgery, 1 h and 24 h after the end of surgery. Plasma concentrations of bupivacaine were measured also in the extradural group at each sampling time. Both techniques provided acceptable analgesia, but the perioperative increases in adrenaline, glucose and ACTH were significantly greater in the opioid group. Noradrenaline concentrations decreased to less than baseline values in the extradural group and were significantly less than in the opioid group. The perioperative increase in cortisol was similar in the two groups, despite the differences in ACTH responses. Most responses returned to the baseline values within 24 h. Plasma bupivacaine concentrations remained within safe limits during the study, but systemic concentrations increased in some of the patients during postoperative infusion with 0.125% bupivacaine.
Lyn is a member of the Src family of protein-tyrosine kinases that can readily undergo autophosphorylation in vitro. The site of autophosphorylation is Tyr397 which corresponds to the consensus autophosphorylation site of other Src family tyrosine kinases. The rate of autophosphorylation is concentration-dependent, indicating that the reaction follows an intermolecular mechanism. Autophosphorylation results in a 17-fold increase in protein-tyrosine kinase activity. Kinetic analysis demonstrates that phosphorylation of a substrate peptide by Lyn following autophosphorylation occurs with a 63-fold decrease in Km but no significant change in Vmax, suggesting that autophosphorylation relieves the conformational constraint that prevents binding of the substrate peptide to the active site of the kinase. Using a phosphotyrosine-containing peptide (pYEEI) that has previously been shown to bind to the Src homology 2 (SH2) domain of Src family tyrosine kinases with high affinity, we found that autophosphorylation results in a significant decrease in accessibility of the Lyn SH2 domain, indicating that conformational changes in the protein kinase domain induced by autophosphorylation can be propagated to the SH2 domain. Our study suggests that autophosphorylation plays an important role in regulating Lyn by modulating both its kinase activity and its interaction with other phosphotyrosine-containing molecules.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.