Role of direct RhoA‐phospholipase D interaction in mediating adenosine‐induced protection from cardiac ischemia

SPECIFIC AIMThe aim of the study was to elucidate the mechanism of protection from myocardial ischemia induced by the adenosine A3 receptor.PRINCIPAL FINDINGSThe adenosine A3 receptor mediates anti-ischemic function in the heart and appears to signal selectively via RhoA and phospholipase D (PLD) to exert its protective effect, different from the cardioprotective mechanism of the adenosine A1 receptor. While a direct RhoA-PLD1 interaction is important in stimulating PLD1 activity, the physiological role of this direct interaction in the intact cell—the cardiac myocyte—is unclear. In an established cardiac myocyte model of preconditioning using cultured chick embryo heart cells, overexpression of the RhoA-noninteracting PLD1 mutant I870R inhibited A3 agonist-induced PLD activation and selectively blocked A3 agonist but not A1 agonist-induced cardioprotection. Atrial cardiac myocytes were rendered null for native adenosine receptors by treatment with irreversible A1 antagonist m-DITC-XAC and selectively tra...