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  • Title: ATP-dependent mechanism for coordination of intercellular Ca2+ signaling and renin secretion in rat juxtaglomerular cells.
    Author: Yao J, Suwa M, Li B, Kawamura K, Morioka T, Oite T.
    Journal: Circ Res; 2003 Aug 22; 93(4):338-45. PubMed ID: 12869388.
    Abstract:
    A change in intracellular Ca2+ is considered to be the common final signaling pathway through which renin secretion is governed. Therefore, information relating to the generation, control, and processing of Ca2+ signaling in juxtaglomerular cells (JG) will be critical for understanding JG cell behavior. In this study, we investigated the means by which JG cells harmonize their intracellular Ca2+ signals and explored the potential role of these mechanisms in renin secretion. Mechanical stimulation of a single JG cell initiated propagation of an intercellular Ca2+ wave to up to 11.9+/-4.1 surrounding cells, and this was prevented in the presence of the ATP-degrading enzyme, apyrase (1.7+/-0.7 cells), or by desensitization of purinergic receptors via pretreatment of cells with ATP (1.8+/-0.9 cells), thus implicating ATP as a mediator responsible for the propagation of intercellular Ca2+ signaling. Consistent with this, JG cells were demonstrated not to express the gap junction protein connexin43, and neither did they possess functional gap junction communication. Furthermore, massive mechanical stretching of JG cells elicited a 3-fold increase in ATP release. Administration of ATP into isolated perfused rat kidneys induced a rapid, potent, and persistent inhibition of renin secretion, together with a transient elevation of renal vascular resistance. ATP (1 mmol/L) caused up to 79% reduction of the renin secretion activated by lowering the renal perfusion flow (P<0.01). Taken together, our results indicate that under mechanical stimulation, ATP functions as a paracellular mediator to regulate renin secretion, possibly through modulating intra- and intercellular Ca2+ signals.
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