Comparison of P2 purinergic receptors of aortic endothelial cells with those of adrenal medulla: evidence for heterogeneity of receptor subtype and of inositol phosphate response

DJ Allsup and MR Boarder

Department of Pharmacology and Therapeutics, University of Leicester, UK.

Vascular endothelial cells from different parts of the circulation are known to show different functional responses, presumably corresponding to physiological roles. Previous studies have shown that ATP acts on P2 purinergic receptors of endothelial cells of major blood vessels, stimulating the formation of inositol phosphates. Here we have compared the action of ATP and congeners acting on endothelial cells of bovine thoracic aorta with cells derived from the microvasculature of bovine adrenal medulla. With measurement of total inositol phosphates, cells from the aorta showed a rank order of agonist potency of 2-methylthio- ATP greater than adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) greater than ADP greater than ATP greater than beta, gamma-imido-ATP greater than beta, gamma-methylene-ATP, consistent with action at receptors of the P2Y subtype. However, with adrenal cells the rank order of potency was ATP gamma S greater than ATP greater than beta, gamma-imido-ATP greater than ADP greater than beta, gamma-methylene-ATP = 2-methylthio-ATP. This profile is not consistent with either P2X or P2Y receptors. When the nature of this inositol phosphate response was analyzed with anion exchange chromatography, it was found that the aortic cells showed an inositol trisphosphate stimulation that peaked within a few seconds and rapidly declined, whereas the response of the adrenal medulla cells continued to rise through 5 min. Analysis of isomers of inositol phosphates revealed a different pattern of metabolism between the two cell types, which may account for the different time course of response. With adrenal cells, ATP at low micromolar concentrations caused a dose-dependent increase in levels of cyclic AMP and had a greater than additive effect on cyclic AMP levels when combined with submaximal stimulation by prostaglandin E2. These results suggest the presence of a P2Y receptor on aortic endothelial cells, with an 'atypical' purinocepter, i.e., neither P2X nor P2Y, on adrenal cells. Furthermore, they show that activation of P2 receptors on the two cell types has different functional consequences.

Volume 38, Issue 1, pp. 84-91, 07/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				D. Hong, D. Jaron, D. G. Buerk, and K. A. Barbee Heterogeneous response of microvascular endothelial cells to shear stress Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2498 - H2508. [Abstract] [Full Text] [PDF]

				D. L. Cioffi, T. M. Moore, J. Schaack, J. R. Creighton, D. M.F. Cooper, and T. Stevens Dominant regulation of interendothelial cell gap formation by calcium-inhibited type 6 adenylyl cyclase J. Cell Biol., June 24, 2002; 157(7): 1267 - 1278. [Abstract] [Full Text] [PDF]

				T. Yamamoto, Y. Habuchi, M. Nishio, J. Morikawa, and H. Tanaka P2 purinoceptors contribute to ATP-induced inhibition of L-type Ca2+ current in rabbit atrial myocytes Cardiovasc Res, January 1, 1999; 41(1): 166 - 174. [Abstract] [Full Text] [PDF]

				S. A. Hartley and R. Z. Kozlowski Electrophysiological Consequences of Purinergic Receptor Stimulation in Isolated Rat Pulmonary Arterial Myocytes Circ. Res., February 1, 1997; 80(2): 170 - 178. [Abstract] [Full Text]

				S. R. Post, J. P. Jacobson, and P. A. Insel P(2) Purinergic Receptor Agonists Enhance cAMP Production in Madin-Darby Canine Kidney Epithelial Cells via an Autocrine/Paracrine Mechanism J. Biol. Chem., January 26, 1996; 271(4): 2029 - 2032. [Abstract] [Full Text] [PDF]

				D. Communi, E. Raspe, S. Pirotton, and J.-M. Boeynaems Coexpression of P2Y and P2U Receptors on Aortic Endothelial Cells : Comparison of Cell Localization and Signaling Pathways Circ. Res., February 1, 1995; 76(2): 191 - 198. [Abstract] [Full Text]