期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 280, 期 6, 页码 F1054-F1061出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.2001.280.6.F1054
关键词
microvascular smooth muscle cells; adeonsine 5 '-triphosphate; afferent arteriole; renal microvasculature; 8,8 '-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5-napthalenetrisulfonic acid hexasodium salt; alpha,beta-methylene-adeonsine 5 '-triphosphate; nifedipine; diltiazem; nickel; calcium channels; P2X receptors
资金
- NIDDK NIH HHS [DK-38226, DK-44628] Funding Source: Medline
This study tested the hypothesis that P2X receptor activation increases intracellular Ca(2+) concentration ([Ca(2+)](i)) in preglomerular microvascular smooth muscle cells (MVSMC) by evoking voltage-dependent calcium influx. MVSMC were obtained and loaded with the calcium-sensitive dye fura 2 and studied by using single-cell fluorescence microscopy. The effect of P2X receptor activation on [Ca(2+)](i) was assessed by using the P2X receptor-selective agonist alpha,beta -methylene-ATP and was compared with responses elicited by the endogenous P2 receptor agonist ATP. alpha,beta -Methylene-ATP increased [Ca(2+)](i) dose dependently. Peak increases in [Ca(2+)](i) averaged 37 +/- 11, 73 +/- 15, and 103 +/- 21 nM at agonist concentrations of 0.1, 1, and 10 muM, respectively. The average peak response elicited by 10 mM alpha,beta -methylene-ATP was similar to 34% of the response obtained with 10 muM ATP. alpha,beta -Methylene-ATP induced a transient increase in [Ca(2+)](i) before [Ca(2+)](i) returned to baseline, whereas ATP induced a biphasic response including a peak response followed by a sustained plateau. In Ca(2+)-free medium, ATP induced a sharp transient increase in [Ca(2+)](i), whereas the response to alpha,beta -methylene-ATP was abolished. Ca(2+) channel blockade with 10 mM diltiazem or nifedipine attenuated the response to alpha,beta -methylene-ATP, whereas nonspecific blockade of Ca(2+) influx pathways with 5 mM Ni(2+) abolished the response. Blockade of P2X receptors with the novel P2X receptor antagonist NF-279 completely but reversibly abolished the response to alpha,beta -methylene-ATP. These results indicate that P2X receptor activation by alpha,beta -methylene-ATP increases [Ca(2+)](i) in preglomerular MVSMC, in part, by stimulating voltage-dependent Ca(2+) influx through L-type Ca(2+) channels.
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