Identification and function of adenosine A₃ receptor in afferent arterioles

Abstract

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.

Genetic Abrogation of Adenosine A 3 Receptor Prevents Uninephrectomy and High Salt–Induced Hypertension

“…All adenosine receptor subtypes have been found in the kidney, but the relative expression of A 3 in renal cortex is low . In agreement with findings by Hansen and colleagues, a recent report suggested rather high expression of the A 3 receptor in microdissected and isolated renal arterioles . Moreover, high abundance of the A 3 receptor has been demonstrated in immune cells, including dendritic cells and lymphocytes, and a role for the A 3 receptor has been suggested in diseases involving inflammation (eg, ischemia reperfusion injury, pain, autoimmune diseases) .…”

“…Moreover, interaction between Ang II and adenosine A 1 or A 2 receptor signaling on the renal arterioles modulates nitric oxide and bioavailability, which has been reported to influence renal hemodynamics during health and in the progression of renal, cardiovascular, and metabolic disorders . Less is known about the A 3 receptor, although a recent study suggested a modulatory role in renal microcirculation. Recent studies also reported that increased adenosine signaling might directly contribute to hypertensive disorders .…”

“…20 In agreement with findings by Hansen and colleagues, a recent report suggested rather high expression of the A 3 receptor in microdissected and isolated renal arterioles. 21 Moreover, high abundance of the A 3 receptor has been demonstrated in immune cells, including dendritic cells and lymphocytes, 15 and a role for the A 3 receptor has been suggested in diseases involving inflammation (eg, ischemia reperfusion injury, pain, autoimmune diseases). 22,23 In addition, accumulating evidence demonstrates that the immune system is directly involved in the pathogenesis and development of both hypertension and CKD.…”

Glucose dilates renal afferent arterioles via glucose transporter-1

“…Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine whether GLUT-1 was expressed in the Af-Art. A single Af-Art was isolated from C57BL/6 mice and transferred to RLT buffer (RNeasy Mini Kit; Qiagen, Venlo, Netherlands) for RNA extraction as we previously described (34,36). The time for dissection was Ͻ30 min after euthanatizing mice to avoid RNA degradation.…”

Adenosine contribution to normal renal physiology and chronic kidney disease

“…Lastly, studies on the effects of A 3 receptor activation on vascular control at the renal beds are scarce. Evidence indicates that activation of the A 3 receptor dilated the norepinephrinepreconstricted afferent arterioles and blunted the vasoconstrictive effect of adenosine A 1 receptor activation (Lu et al 2015). The effects of A 3 receptor activation in other vascular niches are contradictory to date (Hinschen et al 2003;Ansari et al 2007).…”