Parathyroid hormone inhibition of vasopressin-induced vascular smooth muscle contraction.
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)
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
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Schrier
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000096:biosynthesis; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D010716:Phosphatidylinositols; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin; D002118:Calcium