P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb.
Bottom Line: The renal outer medullary K(+) channel (ROMK) is sensitive to intracellular pH where a reduction leads to closing of ROMK.We speculated that P2X receptor stimulation in the TAL could lead to changes in pHi , leading to a reduction in NaCl transport.Typically, Gq -coupled receptors cause a significant acidification of tubular epithelial cells, which was confirmed in this study, by P2Y2 and Ca(2+) sensing receptor stimulation.
Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.Show MeSH
Mentions: Our group previously demonstrated that of the P2Y receptor family, only P2Y2 and P2Y6 are expressed in murine mTAL (Marques et al. 2012). To investigate the role of P2Y receptors in the ATP-induced alkalization, we used the potent P2Y2 receptor agonist UTP that does not activate P2X receptors. Figure3a shows a typical experiment of a perfused mTAL exposed to basolateral UTP (100 μm), causing a small but significant acidification (ΔpHi 0.04 ± 0.01, n = 7, P < 0.001). UDP, a specific P2Y6 receptor agonist, did not cause any changes in pHi (results not shown). The magnitude of the UTP-induced acidification was similar to that seen when 1-μM ATP was applied to the basolateral side (ΔpHi 0.05 ± 0.01, n = 6, Fig.3b), which is sufficient to stimulate the P2Y2 receptor (Abbracchio et al. 2006). Stimulation of the Ca2+ sensing receptors (CaSR) with increased extracellular [Ca2+] (5 mm) also acidified perfused mTALs. These findings indicate that stimulation of Gq-protein-coupled receptors such as P2Y2 and CaSR in the TAL causes a small intracellular acidification.
Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.