Adenosine A1 receptor-operated calcium entry in renal afferent arterioles is dependent on postnatal maturation of TRPC3 channels.

Adenosine A1 receptor-operated calcium entry in renal afferent arterioles is dependent on postnatal maturation of TRPC3 channels.
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腺苷 A1 受体操纵的钙进入肾传入小动脉依赖于出生后 TRPC3 通道的成熟。

DOI:
10.1152/ajprenal.00335.2017
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发表时间:
2017
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Adebiyi,Adebowale
Adebiyi,Adebowale
中科院分区:
--
文献类型:
--
作者:
Soni,Hitesh;Peixoto-Neves,Dieniffer;Buddington,RandalK;Adebiyi,Adebowale

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腺苷是心血管发育和肾功能的调节剂,其通过激活其同源A1受体(A1 Rs)诱导平滑肌细胞(SMC)胞内Ca 2+浓度([Ca 2 +]i)升高来收缩肾传入小动脉。肾血管平滑肌细胞中A1 R依赖性[Ca 2 +] i升高的机制尚未完全解决。肾小球前微血管中A1 R的表达和功能是否依赖于出生后肾脏的成熟还不清楚。在这项研究中,我们表明,选择性激活A1 Rs的2-氯-N6-环戊基腺苷(CCPA)不刺激钙池操作的新生猪传入小动脉内流。然而,CCPA诱导的[Ca 2 +] i升高依赖于磷脂酶C和瞬时受体电位阳离子通道,亚家族C,成员3(TRPC 3)。新生猪(0日龄)传入小动脉的基础[Ca 2 +] i与20日龄猪相比无变化。相比之下,CCPA治疗导致20日龄猪的传入小动脉中的[Ca 2 +] i显著增大。A1 R蛋白在肾脏和传入小动脉的表达水平在0日龄与20日龄猪不变。然而,TRPC 3通道蛋白表达水平在20日龄猪肾脏和传入小动脉中分别高约92%和78%。这些数据表明,激活A1 Rs eliminates受体操作的Ca 2+进入猪传入小动脉,其水平依赖于出生后成熟的TRPC 3通道。我们认为TRPC 3通道可能参与A1 Rs的生理和病理生理过程。
Adenosine, a regulator of cardiovascular development and renal function, constricts renal afferent arterioles by inducing intracellular Ca2+concentration ([Ca2+]i) elevation in smooth muscle cells (SMCs) via activation of its cognate A1receptors (A1Rs). Mechanisms that underlie A1R-dependent [Ca2+]ielevation in renal vascular SMCs are not fully resolved. Whether A1R expression and function in preglomerular microvessels are dependent on postnatal kidney maturation is also unclear. In this study, we show that selective activation of A1Rs by 2-chloro-N6-cyclopentyladenosine (CCPA) does not stimulate store-operated Ca2+entry in afferent arterioles isolated from neonatal pigs. However, CCPA-induced [Ca2+]ielevation is dependent on phospholipase C and transient receptor potential cation channel, subfamily C, member 3 (TRPC3). Basal [Ca2+]iwas 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 [Ca2+]iin afferent arterioles from 20-day-old pigs. A1R 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 A1Rs elicits receptor-operated Ca2+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 A1Rs.
2-氯-N6-环戊基腺苷:A1 腺苷受体的高度选择性激动剂
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