Alterations in dopamine DA1 receptor and G proteins in renal proximal tubules of old rats.
The present study examines the effect of dopamine DA1-receptor agonists on the renal proximal tubular Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity and quantitates DA1 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 DA1-receptor agonist, SKF-38393, produced a concentration-dependent inhibition of Na(+)-K(+)-ATPase activity in proximal tubules from adult rats, whereas the enzyme activity was unaffected by these agonists in the old rats. The binding of DA1-receptor antagonist [3H]Sch-23390 in the proximal tubular basolateral membranes showed a marked decrease (approximately 47%) in the receptor numbers in old compared with adult rats, whereas dissociation constant (Kd) values in old compared with adult rats were not significantly different. Dopamine and SKF-38393 stimulated 35S-labeled guanosine 5'-O-(3-thiotriphosphate) binding in adult rats, but there was no significant effect on the binding in the old rats. Quantification of G2 alpha and Gq/11 alpha using Western analysis revealed a significant increase in quantities of both the G proteins in old rats. The data suggest that a reduction in DA1 receptor number and subsequently reduced G protein activation may be the causative factors for the impairment in DA1 receptor-mediated inhibition of Na(+)-K(+)-ATPase activity in the proximal tubules of old rats.
Kansra
V
V
Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, Texas 77204-5511, USA.
Hussain
T
T
Lokhandwala
M F
MF
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001794:Blood Pressure; D002462:Cell Membrane / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006339:Heart Rate; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012044:Regression Analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*
D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine