Lu Yan, Zhang Rui, Ge Ying, Carlstrom Mattias, Wang Shaohui, Fu Yiling, Cheng Liang, Wei Jin, Roman Richard J, Wang Lei, Gao Xichun, Liu Ruisheng
Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi;
Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida;
Am J Physiol Renal Physiol. 2015 May 1;308(9):F1020-5. doi: 10.1152/ajprenal.00422.2014. Epub 2015 Jan 21.
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.
腺苷在肾微循环调节中发挥重要作用。已在肾脏中发现腺苷的所有受体,即A1、A2A、A2B和A3受体。然而,关于A3受体在肾脏中的定位和功能知之甚少。本研究确定了A3受体在介导传入小动脉(Af-Art)反应中的表达和作用,并研究了A3受体与Af-Art上的血管紧张素II(ANG II)、A1和A2受体之间的相互作用。我们发现,在显微解剖分离的Af-Art中表达了A3受体,且A3受体的mRNA水平为A1的59%。在分离的显微灌注Af-Art中,A3受体激动剂IB-MECA没有收缩作用。A3受体的激活使去甲肾上腺素预收缩的Af-Art舒张,并且分别减弱了腺苷A1受体激活和ANG II对Af-Art的血管收缩作用。选择性A2受体拮抗剂(A2A和A2B均包括)对A3受体激动剂诱导的血管舒张没有影响,表明A3受体激活的舒张作用不是由A2受体激活介导的。我们得出结论,A3受体在Af-Art中表达,且A3受体的激活使Af-Art舒张。