AJP - Cell Physiology, Vol 261, Issue 4 C642-C649, Copyright © 1991 by American Physiological Society
Intracellular pH on adrenergic-stimulated cAMP and cGMP production in rat pinealocytes
A. K. Ho, M. Girard, I. Young and C. L. Chik
Department of Physiology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
In rat pinealocytes, activation of alpha 1-adrenergic receptors leads to
increases in intracellular pH (pHi). In this study, the role of pHi on
adrenergic regulation of cyclic nucleotide accumulation was investigated
using ammonium chloride, which increased pHi, and sodium propionate, which
reduced pHi. Ammonium chloride significantly enhanced the
norepinephrine-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) and
guanosine 3',5'-cyclic monophosphate (cGMP) responses, while it selectively
potentiated the isoproterenol (ISO)-stimulated cGMP response. Reduction of
pHi by sodium propionate reduced the norepinephrine-stimulated cGMP
accumulation by 70%, and its effect on the ISO-stimulated cGMP response was
stimulatory. Treatment with sodium propionate effectively neutralized the
enhancing effects of ammonium chloride on the adrenergic-stimulated cAMP
and cGMP responses. These effects of sodium propionate and ammonium
chloride on cyclic nucleotides appeared to reflect altered rate of
synthesis, and they were also in part secondary to changes in intracellular
Ca2+. Our findings indicate that the receptor-mediated changes in pHi may
play an integral part in the adrenergic regulation of cAMP and cGMP
production in rat pinealocytes.
