AJP - Renal Physiology, Vol 264, Issue 3 453-F457, Copyright © 1993 by American Physiological Society
Parathyroid hormone inhibition of vasopressin-induced vascular smooth muscle contraction
X. Wang, V. A. Briner and R. W. Schrier
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
In various cells, parathyroid hormone (PTH) has been shown to initiate both
polyphosphoinositide (PI) breakdown and activation of adenylate cyclase
(AC). In vascular smooth muscle cells (VSMC), PI hydrolysis is known to
induce contraction, whereas a rise in adenosine 3',5'-cyclic monophosphate
(cAMP) causes relaxation. In the present study, the effect of PTH on
arginine vasopressin (AVP)-induced VSMC contraction and signal transduction
was studied. PTH (10(-7) M) attenuated the percentage of VSMC contracting
in response to AVP (10(-7) M; 40 to 26.5%, P < 0.05). This loss of VSMC
contractility was not the result of PTH-induced changes in AVP receptor
binding. PTH did, however, stimulate VSMC cAMP production in a
dose-dependent manner. The effect of PTH on AVP-induced contraction could
be mimicked by treating VSMC with the cell-permeant cAMP analogue,
8-(4-chlorophenylthio)-cAMP (ClPheScAMP). The effect of PTH on AVP-induced
VSMC contraction was blocked by H-8, an inhibitor of protein kinase A and
thus cAMP production. In parallel to the inhibitory effects of ClPheScAMP
on VSMC contraction, AVP-stimulated inositol trisphosphate production was
also reduced by this permeant cAMP (4,415 to 2,592 cpm/mg protein, P <
0.01). PTH-induced production of cAMP was not blocked by an inhibition of
prostaglandin synthesis [PTH 203 vs. PTH + ibuprofen 161 fmol/micrograms
protein, not significant (NS)]. In contrast, AVP also stimulated cAMP, but
this increase was blocked by ibuprofen.(ABSTRACT TRUNCATED AT 250 WORDS)
