Identification and Function of Adenosine A3 Receptor in Afferent Arterioles

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adenosine, A3 receptor, Af-Art, tubuloglomerular feedback

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Adenosine plays an important role in regulation of renal microcirculation. All receptors of adenosine, A1, A2A, A2B, and A3, have been found in the kidney. However, little is known about the location and function of the A3 receptor in the kidney. The present study determined the expression and role of A3 receptors in mediating the afferent arteriole (Af-Art) response and studied the interaction of A3 receptors with angiotensin II (ANG II), A1 and A2 receptors on the Af-Art. We found that the A3 receptor expressed in microdissected isolated Af-Art and the mRNA levels of A3 receptor were 59% of A1. In the isolated microperfused Af-Art, A3 receptor agonist IB-MECA did not have a constrictive effect. Activation of A3 receptor dilated the preconstricted Af-Art by norepinephrine and blunted the vasoconstrictive effect of both adenosine A1 receptor activation and ANG II on the Af-Art, respectively. Selective A2 receptor antagonist (both A2A and A2B) had no effect on A3 receptor agonist-induced vasodilation, indicating that the dilatory effect of A3 receptor activation is not mediated by activation of A2 receptor. We conclude that the A3 receptor is expressed in the Af-Art, and activation of the A3 receptor dilates the Af-Art.

adenosine is an endogenous adenine nucleoside that is formed by the hydrolysis of ATP. Cellular signaling by adenosine occurs through following receptor subtypes: A1, A2, and A3. The adenosine A2 receptor (A2R) family consists of two subtypes, A2A and A2B (36). All receptors of adenosine have been found in the kidney (1, 16, 20, 37, 41). Adenosine has been suggested as a mediator (via A1 receptor signaling) and a modulator (via A2 receptor) of renal autoregulation (2, 4, 5, 15, 28, 32, 34, 36). In the renal vasculature, adenosine elicits biphasic effects with vasoconstriction via A1 receptors (A1R) at a lower concentration and vasodilation via A2R as the concentration of adenosine increases (14, 27, 33).

Adenosine A3 receptor (A3R) is first found from the rat striatum (40), and it is highly expressed in the lung and liver in humans (22, 31). In kidneys, A3R has been detected both on mRNA and protein levels in various species (7, 22, 23, 26, 30). However, the location and function of the A3R in the kidney are poorly characterized. The objective of the present study is to identify whether A3R is expressed in the afferent arterioles (Af-Art), which are the most important resistant vessels in the kidney (6), and its role in regulating the tone of the Af-Art.

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American Journal of Physiology-Renal Physiology, v. 308, issue 9, p. F1020-F1025