cAMP signaling mechanisms with aging in rats.
Blunted cAMP responses to beta-adrenergic agonists play a major role in diminished smooth muscle relaxation in blood vessels from older animals, although the mechanisms remain uncertain. A diminished cAMP response could potentially arise from changes in the expression of adenylyl cyclase-coupled G proteins, such as a diminished expression of Gs or an increased expression of Gi. We tested the hypothesis that a loss in Gs or increased expression of Gi could occur in tissues such as the aorta, heart and kidney with aging, which would provide a unifying explanation for blunted cAMP responses to many hormones with aging in a variety of cells. Using Western blotting with specific antibodies, we found no generalized changes in G protein expression with aging. Also, injection of pertussis toxin (which functionally inactivates Gi) into older animals did not restore vascular relaxation mediated by beta-adrenergic receptors. We previously found an elevated ratio of regulatory to catalytic subunits of protein kinase A in the aorta of older rats, which would tend to impair activation of the catalytic unit; this alteration was not generalized to other organs such as the heart and kidney. Old rats fed a low salt diet did not show the restored beta-adrenergic agonist-induced vasodilation previously found in elderly humans, suggesting that there are species differences in the development of this deficit. Altogether, these results suggest that altered G protein expression does not provide a general explanation for blunted activation of adenylyl cyclase with aging.
Chin
J H
JH
Department of Medicine, Stanford University School of Medicine and Geriatric Research, Palo Alto, CA 94304, USA.
Hiremath
A N
AN
Hoffman
B B
BB
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002384:Catalysis; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004039:Diet, Sodium-Restricted; D019204:GTP-Binding Proteins / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014664:Vasodilation
D006632:Histamine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D007545:Isoproterenol