Age-related postreceptor mechanisms: changes in adenylate cyclase but not phosphodiesterase in isolated mouse renal medullary collecting ducts.
Urine concentrating ability declines with increasing age, partly due to an impaired response of kidney medullary collecting ducts to the antidiuretic hormone, vasopressin. We investigated this change in isolated mouse medullary collecting ducts by measuring the activity of adenylate cyclase and phosphodiesterase, which catalyse the formation and hydrolysis of cAMP, respectively. Adenylate cyclase activity was measured in the presence of vasopressin (which stimulates adenylate cyclase via the receptor) or forskolin (which directly stimulates the catalytic subunit). We showed an age-related decrease in the catalytic subunit of adenylate cyclase, and no difference in the activity of phosphodiesterase, indicating that a reduction in the catalytic subunit of adenylate cyclase contributes towards the age-related decrease in cyclic AMP response of kidney to vasopressin.
Davidson
Y S
YS
Department of Geriatric Medicine, University Hospital of South Manchester, UK.
Fotheringham
A P
AP
Davies
I
I
Morris
J A
JA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism*
D010726:Phosphodiesterase Inhibitors; D017483:Receptors, Vasopressin; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine