Effect of age on parathyroid hormone and forskolin stimulated adenylate cyclase and protein kinase activity in the renal cortex.
The capacity of parathyroid hormone (PTH) to stimulate the renal production of 1,25-dihydroxyvitamin D declines with age. Since the action of PTH in the kidney is mediated by cAMP, we have examined the effect of PTH and forskolin on renal cortical adenylate cyclase in young (3 months), adult (13-15 months), and old (25-27 months) F344 rats. PTH-dependent adenylate cyclase, measured as cAMP accumulation in cortical slices, was reduced in adult and old rats compared to young rats over a PTH concentration range of 0.015-15 units/ml. There was no difference in PTH-dependent adenylate cyclase activity between adult and old rats. Renal plasma membrane preparations demonstrated similar changes in PTH-stimulated adenylate cyclase activity. There was no difference in calcitonin, forskolin, or guanyl-5-ylimidodiphosphate (Gpp(NH)p) stimulation of adenylate cyclase in plasma membranes from each age group, suggesting that the defect lies in the membrane receptor for PTH. The decreased adult sensitivity to PTH could be reversed by thyroparathyroidectomy. PTH stimulation of cytosolic protein kinase activity did not change with age. These results suggest that the decrease in PTH-dependent adenylate cyclase is due to the alterations at the level of PTH receptor. These alterations may be in response to the increase in serum PTH seen in these animals with increasing age.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone
D010281:Parathyroid Hormone; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D005576:Colforsin; D000242:Cyclic AMP; D011494:Protein Kinases; D000262:Adenylyl Cyclases