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