ALTERATIONS IN DOPAMINE DA(1) RECEPTOR AND G-PROTEINS IN RENAL PROXIMAL TUBULES OF OLD RATS

The present study examines the effect of dopamine DA(1)-receptor agoni sts on the renal proximal tubular Na+-K+-adenosinetriphosphatase (Na+- K+-ATPase) activity and quantitates DA(1) receptors and the coupled G proteins in Fischer 344 model of adult (6 mo old) and old (23 mo old) rats. Dopamine and the preferential DA(1)-receptor agonist, SKF-38393, produced a concentration-dependent inhibition of Na+-K+-ATPase activi ty in proximal tubules from adult rats, whereas the enzyme activity wa s unaffected by these agonists in the old rats. The binding of DA(1)-r eceptor antagonist [H-3]Sch-23390 in the proximal tubular basolateral membranes showed a marked decrease (similar to 47%) in the receptor nu mbers in old compared with adult rats, whereas dissociation constant ( K-d) values in old compared with adult rats were not significantly dif ferent. Dopamine and SKF-38393 stimulated S-35-labeled guanosine 5'-O- (3-thiotriphosphate) binding in adult rats, but there was no significa nt effect on the binding in the old rats. Quantification of G(s) alpha and G(q/11 alpha) using Western analysis revealed a significant incre ase in quantities of both the G proteins in old rats. The data suggest that a reduction in DA(1) receptor number and subsequently reduced G protein activation may be the causative factors for the impairment in DA(1) receptor-mediated inhibition of Na+-K+-ATPase activity in the pr oximal tubules of old rats.