AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 4 726-R732, Copyright © 1993 by American Physiological Society

ARTICLES

Organ specificity of the dopamine1 receptor/adenylyl cyclase coupling defect in spontaneously hypertensive rats

R. A. Felder, S. Kinoshita, K. Ohbu, M. M. Mouradian, D. R. Sibley, F. J. Monsma Jr, T. Minowa, M. T. Minowa, L. M. Canessa and P. A. Jose
Department of Pathology, University of Virginia, Charlottesville 22908.

The coupling between the dopamine1 (DA1) receptor and the G protein/adenylyl cyclase (AC) enzyme complex is defective in the proximal convoluted tubule (PCT) of 20-wk-old spontaneously hypertensive rats (SHRs). Because this coupling defect could have been due to desensitization secondary to elevated renal dopamine levels in the adult animal, we studied the interaction between DA1 receptors and AC in PCT of rats as early as 3 wk of age, a time when renal dopamine levels are similar in SHRs and their normotensive controls (Wistar-Kyoto rats, WKYs). Maximum receptor density did not change with age and was similar in WKYs and SHRs in all the age groups studied (3, 8, and 20 wk). Basal-, forskolin-, and guanyl nucleotide-stimulated AC activities were also similar in WKYs and SHRs and did not change with age. However, the DA1 agonist-stimulated AC activity was greater in WKYs than in SHRs and increased with age in WKYs but not in SHRs. Moreover, the ability of a nonhydrolyzable analogue of GTP, Gpp(NH)p, to enhance DA1 agonist (SND-919-C12, 1 microM)-stimulated AC activity increased with age in WKY but not in SHRs. To determine if the defect noted in the PCT of SHRs is due to a defective D1A receptor gene, parallel studies were performed in the striatum, since this receptor is expressed predominantly in the latter tissue. In contrast to the results in PCT, radioligand binding and AC studies in striatum revealed no differences between WKYs and SHRs.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				C. Zeng, I. Armando, Y. Luo, G. M. Eisner, R. A. Felder, and P. A. Jose Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H551 - H569. [Abstract] [Full Text] [PDF]

				C. Zeng, H. Sanada, H. Watanabe, G. M. Eisner, R. A. Felder, and P. A. Jose Functional genomics of the dopaminergic system in hypertension Physiol Genomics, November 17, 2004; 19(3): 233 - 246. [Abstract] [Full Text] [PDF]

				R. Pedrosa, P. Gomes, U. Hopfer, P. A. Jose, and P. Soares-da-Silva Gi{alpha}3 protein-coupled dopamine D3 receptor-mediated inhibition of renal NHE3 activity in SHR proximal tubular cells is a PLC-PKC-mediated event Am J Physiol Renal Physiol, November 1, 2004; 287(5): F1059 - F1066. [Abstract] [Full Text] [PDF]

				R. Pedrosa, P. A. Jose, and P. Soares-da-Silva Defective D1-like receptor-mediated inhibition of the Cl-/HCO3- exchanger in immortalized SHR proximal tubular epithelial cells Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1120 - F1126. [Abstract] [Full Text] [PDF]

				E. K. Jackson, Z. Mi, C. Zhu, and R. K. Dubey Adenosine Biosynthesis in the Collecting Duct J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 888 - 896. [Abstract] [Full Text] [PDF]

				T. Hussain and M. F. Lokhandwala Renal Dopamine Receptors and Hypertension Experimental Biology and Medicine, February 1, 2003; 228(2): 134 - 142. [Abstract] [Full Text] [PDF]

				X. X. Li, J. Xu, S. Zheng, F. E. Albrecht, J. E. Robillard, G. M. Eisner, and P. A. Jose D1 dopamine receptor regulation of NHE3 during development in spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1650 - R1656. [Abstract] [Full Text] [PDF]

				P. Yu, L. D. Asico, G. M. Eisner, U. Hopfer, R. A. Felder, and P. A. Jose Renal Protein Phosphatase 2A Activity and Spontaneous Hypertension in Rats Hypertension, December 1, 2000; 36(6): 1053 - 1058. [Abstract] [Full Text] [PDF]

				X. X. Li, F. E. Albrecht, J. E. Robillard, G. M. Eisner, and P. A. Jose Gbeta regulation of Na/H exchanger-3 activity in rat renal proximal tubules during development Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2000; 278(4): R931 - R936. [Abstract] [Full Text] [PDF]

				T. Hussain, S. A. Beheray, and M. F. Lokhandwala Defective Dopamine Receptor Function in Proximal Tubules of Obese Zucker Rats Hypertension, November 1, 1999; 34(5): 1091 - 1096. [Abstract] [Full Text] [PDF]

				X. Ruan, C. Chatziantoniou, and W. J. Arendshorst Impaired Prostaglandin E2/Prostaglandin I2 Receptor-Gs Protein Interactions in Isolated Renal Resistance Arterioles of Spontaneously Hypertensive Rats Hypertension, November 1, 1999; 34(5): 1134 - 1140. [Abstract] [Full Text] [PDF]

				J. Zicha and J. Kunes Ontogenetic Aspects of Hypertension Development: Analysis in the Rat Physiol Rev, October 1, 1999; 79(4): 1227 - 1282. [Abstract] [Full Text] [PDF]

				D. Sun, T. W. Wilborn, and J. A. Schafer Dopamine D4 receptor isoform mRNA and protein are expressed in the rat cortical collecting duct Am J Physiol Renal Physiol, November 1, 1998; 275(5): F742 - F751. [Abstract] [Full Text] [PDF]

				T. Hussain and M. F. Lokhandwala Renal Dopamine Receptor Function in Hypertension Hypertension, August 1, 1998; 32(2): 187 - 197. [Abstract] [Full Text] [PDF]

				H. Brismar, M. Asghar, R. M. Carey, P. Greengard, and A. Aperia Dopamine-induced recruitment of dopamine D1 receptors to the plasma membrane PNAS, May 12, 1998; 95(10): 5573 - 5578. [Abstract] [Full Text] [PDF]

				C. MISSALE, S. R. NASH, S. W. ROBINSON, M. JABER, and M. G. CARON Dopamine Receptors: From Structure to Function Physiol Rev, January 1, 1998; 78(1): 189 - 225. [Abstract] [Full Text] [PDF]

				D. P. O'Connell, A. M. Aherne, E. Lane, R. A. Felder, and R. M. Carey Detection of dopamine receptor D1A subtype-specific mRNA in rat kidney by in situ amplification Am J Physiol Renal Physiol, January 1, 1998; 274(1): F232 - F241. [Abstract] [Full Text] [PDF]

				A. Ricci, E. Bronzetti, P. Mulatero, M. Schena, F. Veglio, and F. Amenta Dopamine D3 Receptor in Peripheral Mononuclear Cells of Essential Hypertensives Hypertension, December 1, 1997; 30(6): 1566 - 1571. [Abstract] [Full Text]

				I. Yamaguchi, L. Yao, H. Sanada, R. Ozono, M. M. Mouradian, P. A. Jose, R. M. Carey, and R. A. Felder Dopamine D1A Receptors and Renin Release in Rat Juxtaglomerular Cells Hypertension, April 1, 1997; 29(4): 962 - 968. [Abstract] [Full Text]

				M. C. Hu, L. Fan, L. A. Crowder, Z. Karim-Jimenez, H. Murer, and O. W. Moe Dopamine Acutely Stimulates Na+/H+ Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles. DEPENDENCE ON PROTEIN KINASE A-MEDIATED NHE3 PHOSPHORYLATION J. Biol. Chem., July 13, 2001; 276(29): 26906 - 26915. [Abstract] [Full Text] [PDF]