Adenosine receptor specificity in preconditioning of isolated rabbit cardiomyocytes: evidence of A3 receptor involvement

Abstract

Preconditioning can be induced in isolated myocytes by a 5 min preincubation/30 min postincubation protocol, and a similar protection induced by adenosine agonists with A3, but not A1 selectivity. Preconditioning is blocked by non-selective or selective A1/A3 adenosine antagonists and a specific protein kinase C inhibitor, but not by A1 antagonists with little affinity for A3 receptors. The results suggest that preconditioning in isolated rabbit myocytes requires participation of adenosine receptors with agonist/antagonist binding characteristics of the A3 subtype, and is likely to be mediated by activation of protein kinase C.

Activation of ɛ protein kinase C correlates with a cardioprotective effect of regular ethanol consumption

“…One potential mechanism by which regular drinking may improve survival after MI is to reduce ischemia-reperfusion injury, analogous to experimental ischemic preconditioning (15)(16)(17)(18)(19). The studies in guinea pigs described here show that regular ethanol consumption mimics ischemic preconditioning and reduces ischemiareperfusion injury.…”

“…We recently found that regular ethanol consumption induces long-term protection against ischemia-reperfusion injury in guinea pig hearts (14). We showed that this cardioprotective effect of ethanol requires adenosine A 1 receptor activation at the time of ischemia (14), like experimental ischemic preconditioning (15)(16)(17)(18)(19). Ischemic preconditioning occurs when brief periods of ischemia and reperfusion protect hearts against injury from subsequent prolonged ischemia-reperfusion.…”

Direct preconditioning of cultured chick ventricular myocytes. Novel functions of cardiac adenosine A2a and A3 receptors.

“…The preconditioning effect of A 3 agonists was not blocked by DPCPX while that induced by the A 1 agonist CCPA was completely inhibited by this xanthine, similar to the results obtained in the cAMP study. Previous studies (15,38) indicated the potential presence of a non-A 1 subtype, possibly an A 3 receptor, on the rabbit myocardium. However, the present study, utilizing a novel ventricular cell model of preconditioning, provides the first conclusive evidence that the adenosine A 3 receptor is present on the ventricular myocyte and that in addition to the A 1 receptor, A 3 receptor activation can also simulate the cardioprotective effect of preconditioning.…”

“…Adenosine is released in large amounts during myocardial ischemia and has been demonstrated to play a major role in mediating preconditioning and other cardioprotective effects in most animal species, including humans (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Previous studies (15)(16)(17) of adult human and rabbit ventricular myocytes and cultured neonatal rat cardiac myocytes provided important insight by indicating that the cardioprotective mechanism of preconditioning is exerted, at least in part, at the level of and by the cardiac myocytes in the intact heart. Although a non-A 1 receptor, possibly the A 3 subtype, may be involved in mediating preconditioning, very little is known regarding the role of different adenosine receptor subtypes in mediating or modulating preconditioning of the cardiac myocytes.…”

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

“…Additionally, cardiac cell isolation is a complex, multi-step process. 18 Therefore H9c2, a commercially available myogenic cell line derived from embryonic rat heart ventricle, 19 and which has reportedly comparable levels of drug metabolising enzymes, 20 provides a valuable in vitro alternative to the use of rat hearts and thus reducing reliance on in vivo research. This may contribute, at least in some way, to the 3Rs philosophy (reduction, refinement, and replacement of animal experiments), 21 which is also in line with a national centred UK government-sponsored scientific organisation, NC3Rs.…”