AJP - Cell Physiology, Vol 263, Issue 5 C941-C947, Copyright © 1992 by American Physiological Society
Acute variations in extracellular pH modulate transduction pathways of PTH in rat proximal tubule
J. Poggioli, G. Lazar, P. Houillier, J. P. Gardin and M. Paillard
Institut National de la Sante et de la Recherche Medicale U.356, Departement de Physiologie, Universite Pierre et Marie Curie, Paris, France.
An increase in circulating parathyroid hormone (PTH) has been shown to
enhance the capacity for the kidney to excrete an acid as well an alkaline
load, which suggests that changes in systemic acid-base status may modulate
the effect of the hormone on bicarbonate absorption in proximal tubule. In
the present study, we tested the possibility that acute variations in
extracellular pH (pHe), obtained by modifying bicarbonate concentration at
constant PCO2 (40 mmHg), may modulate the responses of intracellular
messengers coupled to PTH receptors in a preparation of freshly isolated
proximal tubule fragments. Variations in pHe, which induced parallel
variations in intracellular pH (pHi), did not affect unstimulated values
for adenosine 3',5'-cyclic monophosphate (cAMP) production, inositol
trisphosphate accumulation, or cytosolic free Ca2+ concentration. In
contrast, reducing pHe from 7.4 to 7.2 elicited a decrease of the
PTH-induced cAMP production, whereas increasing pHe from 7.4 to 7.6
enhanced it. The ability for cholera toxin and forskolin (which both bypass
PTH receptors) to stimulate cAMP formation was diminished at pHe 7.2 and
enhanced at pHe 7.6 (the increase did not achieve statistical significance
in the presence of forskolin), suggesting that variations in pHe and/or pHi
may affect per se adenylyl cyclase activity. Conversely, reducing pHe from
7.4 to 7.2 enhanced the PTH-induced inositol trisphosphate accumulation and
rise in cytosolic free Ca2+ whereas increasing pHe from 7.4 to 7.6 had
opposite effects.(ABSTRACT TRUNCATED AT 250 WORDS)
