Laske-Ernst Julia, Stehle Alexander, Vallon Volker, Quast Ulrich, Russ Ulrich
Department of Pharmacology and Toxicology, Medical Faculty, University of Tübingen, Tübingen, Germany.
Kidney Blood Press Res. 2008;31(2):94-103. doi: 10.1159/000119712. Epub 2008 Mar 6.
Renin is mainly secreted from the juxtaglomerular cells (JGC) in the kidney situated in the afferent arteriole close to the vessel pole. Angiotensin II (ANG II) and adenosine inhibit renin secretion and synergistically constrict the afferent arteriole. ANG II depolarises JGC and increases the cytoplasmic free Ca2+ concentration [Ca2+]i. The responses of JGC to adenosine are less known.
Effects of adenosine on membrane potential and [Ca2+]i were studied in afferent arterioles from NaCl-depleted rats and mice.
Stimulation of A1 adenosine receptors (A1AR) by adenosine (10 microM) or cyclohexyladenosine (1 microM) increased the spiking frequency of JGC, slightly depolarised the cells and, in < or =50% of the cases, increased [Ca2+]i. These effects were much smaller than those of ANG II (3 nM). Simultaneous application of cyclohexyladenosine and ANG II gave only additive effects on [Ca2+]i; in addition, responses to ANG II in JGC from A1AR knockout mice were similar to those from control mice.
The small changes in membrane potential and [Ca2+]i in response to A1AR stimulation as compared to those of ANG II may suggest that these 2 tissue hormones use different signal transduction mechanisms to affect JGC function, including the inhibition of renin release.
肾素主要由位于入球小动脉靠近血管极处的肾脏球旁细胞(JGC)分泌。血管紧张素II(ANG II)和腺苷抑制肾素分泌,并协同收缩入球小动脉。ANG II使JGC去极化并增加细胞质游离Ca2+浓度[Ca2+]i。JGC对腺苷的反应了解较少。
研究了腺苷对缺钠大鼠和小鼠入球小动脉膜电位和[Ca2+]i的影响。
腺苷(10微摩尔)或环己基腺苷(1微摩尔)刺激A1腺苷受体(A1AR)增加JGC的放电频率,使细胞轻度去极化,并且在≤50%的情况下增加[Ca2+]i。这些效应远小于ANG II(3纳摩尔)的效应。同时应用环己基腺苷和ANG II对[Ca2+]i仅产生相加效应;此外,A1AR基因敲除小鼠JGC对ANG II的反应与对照小鼠相似。
与ANG II相比,A1AR刺激引起的膜电位和[Ca2+]i的微小变化可能表明这两种组织激素使用不同的信号转导机制来影响JGC功能,包括抑制肾素释放。