pH dependence of the action of arginine vasopressin in renal collecting tubule

Abstract

We determined whether extracellular pH (pHe) and intracellular pH (pHi) modulate the cellular actions of arginine vasopressin (AVP) in rat renal papillary collecting tubule cells in culture. AVP significantly increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) production and cellular free calcium concentration ([Ca2+]i). pHe ranging from 6.8 to 8.0 distributed the pHi between 6.94 and 7.27. The acidified pHe reduced the AVP- and forskolin-induced cAMP production, the AVP-mobilized [Ca2+]i, and [3H]AVP receptor binding, and the alkalinized pHe enhanced the AVP- and forskolin-produced cAMP. Intracellular acidification occurred under three different conditions as follows: using carbonyl cyanide-m-chlorophenylhydrazone (CCCP), acetate buffer, and bicarbonate buffer with a reduced concentration of bicarbonate. Intracellular acidification significantly diminished both the AVP- and forskolin-induced increases in cAMP production and the AVP-mobilized [Ca2+]i but did not alter [3H]AVP receptor binding. Intracellular alkalinization by NH4Cl or chloride-free bicarbonate buffer, in contrast, augmented them. These results indicate that alterations in pHi modulate the cellular action of AVP to produce cAMP and mobilize [Ca2+]i in renal papillary collecting tubule cells. Also, reduced receptor binding of AVP is involved in the mechanism of the effects of low pHe.