This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hanson, A. S. Articles by Linas, S. L. Search for Related Content PubMed PubMed Citation Articles by Hanson, A. S. Articles by Linas, S. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL PARATHYROID HORMONE

Hypertension, Vol 23, 468-475, Copyright © 1994 by American Heart Association

ARTICLES

Parathyroid hormone/adenylate cyclase coupling in vascular smooth muscle cells

AS Hanson and SL Linas
Denver General Hospital Center, CO 80204-4507.

Parathyroid hormone (PTH) has been implicated in hypertension, but PTH infusion results in vasodilation. PTH activates adenylate cyclase in vascular smooth muscle, but little is known about the factors that regulate PTH receptor/adenylate cyclase coupling in vascular cells. To characterize hormone-receptor signaling, we measured cyclic AMP levels in rat arterial smooth muscle cells in culture exposed to PTH (bovine 1- 34). PTH yielded time- and concentration-dependent increases in cyclic AMP levels. Compared with isoproterenol, PTH was more potent, with a threshold at 2 x 10(-9) versus 5 x 10(-8) mol/L and half maximal responses at 10(-8) versus 2.4 x 10(-7) mol/L. PTH-induced increases in cyclic AMP were independent of extracellular calcium, cyclooxygenase metabolites, phospholipase C, and protein kinase C because PTH-induced increases in cyclic AMP were not prevented by variations in extracellular calcium, indomethacin, angiotensin II, vasopressin, and protein kinase C activators or inhibitors. PTH/adenylate cyclase coupling was G protein-dependent because increases in cyclic AMP were prevented by preincubation with cholera toxin but not with pertussis toxin. Prolonged exposure to PTH resulted in time- and concentration- dependent homologous desensitization of cyclic AMP responses. Desensitization occurred proximal to G protein/adenylate cyclase because after prolonged PTH, responses to forskolin and cholera toxin remained intact. Desensitization was independent of protein kinase A and receptor sequestration because cyclic AMP responses remained after prolonged exposure to forskolin and pretreatment with phenylarsine oxide, colchicine, and cytochalasin D. We conclude that in vascular smooth muscle cells, PTH is coupled to adenylate cyclase through a cholera toxin-sensitive G protein.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				D. Somjen, Y. Weisman, F. Kohen, B. Gayer, R. Limor, O. Sharon, N. Jaccard, E. Knoll, and N. Stern 25-Hydroxyvitamin D3-1{alpha}-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds Circulation, April 5, 2005; 111(13): 1666 - 1671. [Abstract] [Full Text] [PDF]

				P. Andersson, E. Rydberg, and R. Willenheimer Primary hyperparathyroidism and heart disease -- a review Eur. Heart J., October 2, 2004; 25(20): 1776 - 1787. [Abstract] [Full Text] [PDF]

				F. Fallo, G. Camporese, E. Capitelli, G. M. Andreozzi, F. Mantero, and F. Lumachi Ultrasound Evaluation of Carotid Artery in Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2096 - 2099. [Abstract] [Full Text] [PDF]

				S. J. Marchais, F. Metivier, A. P. Guerin, and G. M. London Association of hyperphosphataemia with haemodynamic disturbances in end-stage renal disease Nephrol. Dial. Transplant., September 1, 1999; 14(9): 2178 - 2183. [Abstract] [Full Text] [PDF]

				G. Picotto, V. Massheimer, and R. Boland Parathyroid hormone stimulates calcium influx and the cAMP messenger system in rat enterocytes Am J Physiol Cell Physiol, October 1, 1997; 273(4): C1349 - C1353. [Abstract] [Full Text] [PDF]