EFFECT OF INHIBITORS OF PROTEIN KINASE C(PKC) AND PROTEIN TYROSINE KINASE(PTK) ON THE CEREBROVASCULAR RESPONSE TO ADENOSINE 2276

Adenosine is an important factor in cerebrovascular regulation in the newborn especially under conditions low cerebral oxygen availability. Post receptor signaling associated with adenosine receptor(s) in the newborn cerebral circulation are poorly understood. Recent studies suggest that certain adenosine receptors are coupled to PKC-and/or PTK-dependent signal transduction pathways. We evaluated the hypothesis that activation of PKC modulates the cerebrovascular response to adenosine in vivo by examining the effect of staurosporine, an inhibitor of PKC, using the closed cranial window preparation in twelve newborn piglets. In that paradigm, staurosporine (9 nM) treatment augmented by 4-fold the increase pial arteriolar diameter induced by 1 μM exogenous adenosine (Δdiameter control = 4±2%[79±4 μm to 82±3 μm]; Δdiameter staurosporine = 17±3%[56±3 μm to 101±5 μm]). In addition, the adenosine-induced vasodilation was prolonged in staurosporine-treated preparations. Recent experiments show a similar effect, i.e., enhanced the dose-dependent relaxation response to adenosine in isolated, newborn lamb middle cerebral artery (MCA) preparations in tissue bath. An inhibitor of PTK (genistein, 20 μM) showed similar trend but was not statistically significant. The data suggest that activation of staurosporine-sensitive signal transduction pathways such as PKC may play a role in the ultimate expression of contractile properties of cerebral arteries from newborn animal models. We propose that certain adenosine receptors activate PKC which modulate the contraction/relaxation response and/or modify adenosine uptake and metabolism. (Supported by the American Heart Association national council, #95009270)

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Wagerle, L., Kim, S. & Russo, P. EFFECT OF INHIBITORS OF PROTEIN KINASE C(PKC) AND PROTEIN TYROSINE KINASE(PTK) ON THE CEREBROVASCULAR RESPONSE TO ADENOSINE 2276. Pediatr Res 39, 382 (1996). https://doi.org/10.1203/00006450-199604001-02301

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