Soni Hitesh, Peixoto-Neves Dieniffer, Buddington Randal K, Adebiyi Adebowale
Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
School of Health Studies, University of Memphis, Memphis, Tennessee.
Am J Physiol Renal Physiol. 2017 Dec 1;313(6):F1216-F1222. doi: 10.1152/ajprenal.00335.2017. Epub 2017 Aug 30.
Adenosine, a regulator of cardiovascular development and renal function, constricts renal afferent arterioles by inducing intracellular Ca concentration ([Ca]) elevation in smooth muscle cells (SMCs) via activation of its cognate A receptors (ARs). Mechanisms that underlie AR-dependent [Ca] elevation in renal vascular SMCs are not fully resolved. Whether AR expression and function in preglomerular microvessels are dependent on postnatal kidney maturation is also unclear. In this study, we show that selective activation of ARs by 2-chloro--cyclopentyladenosine (CCPA) does not stimulate store-operated Ca entry in afferent arterioles isolated from neonatal pigs. However, CCPA-induced [Ca] elevation is dependent on phospholipase C and transient receptor potential cation channel, subfamily C, member 3 (TRPC3). Basal [Ca] was unchanged in afferent arterioles isolated from newborn (0-day-old) pigs compared with their 20-day-old counterparts. By contrast, CCPA treatment resulted in significantly larger [Ca] in afferent arterioles from 20-day-old pigs. AR protein expression levels in the kidneys and afferent arterioles were unaltered in 0- vs. 20-day-old pigs. However, the TRPC3 channel protein expression level was ~92 and 78% higher in 20-day-old pig kidneys and afferent arterioles, respectively. These data suggest that activation of ARs elicits receptor-operated Ca entry in porcine afferent arterioles, the level of which is dependent on postnatal maturation of TRPC3 channels. We propose that TRPC3 channels may contribute to the physiology and pathophysiology of ARs.
腺苷作为心血管发育和肾功能的调节因子，通过激活其同源A受体（ARs）诱导平滑肌细胞（SMCs）内细胞钙浓度（[Ca]）升高，从而使肾入球小动脉收缩。肾血管平滑肌细胞中AR依赖性[Ca]升高的机制尚未完全明确。肾小球前微血管中AR的表达和功能是否依赖于出生后肾脏的成熟也不清楚。在本研究中，我们发现2-氯-环戊基腺苷（CCPA）对ARs的选择性激活不会刺激从新生猪分离的入球小动脉中的储存式钙内流。然而，CCPA诱导的[Ca]升高依赖于磷脂酶C和瞬时受体电位阳离子通道C亚家族成员3（TRPC3）。与20日龄的猪相比，从新生（0日龄）猪分离的入球小动脉中的基础[Ca]没有变化。相比之下，CCPA处理使20日龄猪的入球小动脉中的[Ca]显著升高。0日龄和20日龄猪的肾脏和入球小动脉中AR蛋白表达水平没有改变。然而，20日龄猪的肾脏和入球小动脉中TRPC3通道蛋白表达水平分别高出约92%和78%。这些数据表明，ARs的激活在猪入球小动脉中引发受体操纵的钙内流，其水平依赖于TRPC3通道的出生后成熟。我们提出，TRPC3通道可能参与ARs的生理和病理生理过程。
