Ischaemic preconditioning and postconditioning do not affect adenosine A(1) and A (2A) receptor sensitivity.

摘要

Endogenous adenosine is an important mediator of ischae-mic preconditioning and postconditioning. The protective effect of ischaemic preconditioning is dependent on activation of adenosine A_1 receptors in the first few minutes of reperfusion 1. In contrast, the infarct size-limiting effect of ischaemic postconditioning is mediated by the activation of adenosine A_(2A) and A_(2B) receptors at the time of reperfusion 2, 3. Paradoxically, although the cardio-protective effect of preconditioning and postconditioning are critically dependent on adenosine receptor stimulation immediately after reperfusion, several research groups could not demonstrate an infarct size-limiting effect of administration of exogenous adenosine at the moment of reperfusion 4-6, A possible explanation is that the pre-and postconditioning stimuli increase the sensitivity of a specific adenosine receptor sub-type. Indeed, this mecha nism was recently proposed for the adenosine A_(2B) receptor 7. The A_(2B) receptor has a K_m value for adenosine that is much higher than the endogenous adenosine concentration reached during ischaemia. Kuno et al have recently shown in the rabbit heart that brief preconditioning ischaemia markedly lowered the threshold for an adenosine A_(2B) agonist to increase the phosphorylation of the kinases, Akt and Erk1/2 7.