Blockade Of A2A Receptors Research Articles

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

Preconditioning with brief ischemia before a sustained period of ischemia reduces infarct size in the perfused heart. A cultured chick ventricular myocyte model was developed to investigate the role of adenosine receptor subtypes in cardiac preconditioning. Brief hypoxic exposure, termed preconditioning hypoxia, prior to prolonged hypoxia, protected myocytes against injury induced by the prolonged hypoxia. Activation of the adenosine A1 receptor with CCPA or the A3 receptor with C1-IB-MECA can replace preconditioning hypoxia and simulate preconditioning, with a maximal effect at 100 nM. While activation of the A2a receptor by 1 microM CGS21680 could not mimic preconditioning, its stimulation during preconditioning hypoxia, however, attenuated the protection against hypoxia-induced injury. Blockade of A2a receptors with the selective antagonist CSC (1 microM) during preconditioning hypoxia enhanced the protective effect of preconditioning. Nifedipine, which blocked the A2a receptor-mediated calcium entry, abolished the A2a agonist-induced attenuation of preconditioning. Isoproterenol, forskolin, and BayK 8644, which stimulated calcium entry, also attenuated preconditioning. Nifedipine blocked the increase in calcium uptake by these agents as well as their attenuating effect on preconditioning. The present study provides the first evidence that the adenosine A3 receptor is present on ventricular myocytes and can mediate simulation of preconditioning. The data demonstrate, for the first time, that activation of the A2a receptor antagonizes the preconditioning effect of adenosine, with increased calcium entry during the preconditioning stimuli as a novel mechanism.

P-146 - Blockade of adenosine A2a receptors potentiates dopamine agonist-induced rotation in rats with unilateral 6-hydroxydopamine lesions of nigrostriatal pathway.

P-146 - Blockade of adenosine A2a receptors potentiates dopamine agonist-induced rotation in rats with unilateral 6-hydroxydopamine lesions of nigrostriatal pathway.

Relationship between A 1 adenosine receptors and protein kinase C activity in the control of purine release from rat cultured astrocytes

We reported that inhibition of central sympathetic pools of imidazoline I1 receptors abolishes the hypotensive effect of ethanol in rats with glycerol-induced acute renal failure (ARF). This study investigated whether adenosine receptors modulate the ethanol-I1-receptor interaction. The effect of selective blockade of adenosine A1, A2A, or A2B receptors on hemodynamic responses to ethanol in the absence and presence of the I1-receptor agonist moxonidine was determined in ARF rats. Ethanol (1 g/kg i.v.) decreased and increased blood pressure (BP) and heart rate (HR), respectively. Pretreatment with moxonidine abolished the hypotensive but not the tachycardic effect of ethanol. The hypotensive effect of ethanol remained unaltered after selective blockade of A1, A2A, or A2B receptors with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 8-(3-chlorostyryl) caffeine (CSC) and alloxazine, respectively. Neither was ethanol hypotension affected after inhibition of adenosine uptake by dipyridamole (DPY). Alternatively, the ability of moxonidine to abolish ethanol hypotension was still evident in presence of alloxazine whereas it disappeared or weakened in rats pretreated with CSC and DPCPX, respectively. These findings implicate adenosine A2A receptors in the moxonidine-evoked inhibition of the hypotensive action of ethanol. A modulatory role for adenosine A1 site in the ethanol-I1-receptor interaction is also possible through as yet unidentified mechanism.