Differential effects of chlorpropamide on the control of adenosine 3',5'-monophosphate metabolism in rat renal cortex and medulla

Leichter, S.B.; Chase, L.R.

Endocrinology 102(3): 785-790

1978


ISSN/ISBN: 0013-7227
PMID: 217601
DOI: 10.1210/endo-102-3-785
Accession: 068524447

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Abstract
Chlorpropamide potentiates the renal effects of vasopressin in patients with partial diabetes insipidus and blunts the renal effects of parathyroid hormone. To explain these actions, the effects of chlorpropamide were tested on adenylate cyclase activity, cAMP concentration and cyclic nucleotide phosphodiesterase activity in rat renal cortex and medulla. In renal medulla, chlorpropamide inhibited adenylate cyclase activity at 5 .times. 10-3 M and phosphodiesterase activity at 5 .times. 10-4 M. In slices from medulla, preincubation with chlorpropamide had no effect on basal cAMP concentration, but markedly potentiated the increase in cAMP in response to vasopressin. The degree of potentiation was a function of the concentration of chlorpropamide tested. In renal cortex, chlorpropamide inhibited adenylate cyclase activity at 5 .times. 10-3 M, but had no effect on phosphodiesterase at this or lower concentrations. In slices from cortex, preincubation with chlorpropamide had no effect on basal cAMP concentration but significantly blunted the increase in cAMP in response to parathyroid hormone. These results indicate that differential effects of the drug on adenylate cyclase and phosphodiesterase activity in renal cortex and medulla result in changes in cAMP concentration that differ in the 2 areas of the kidney. The net increase in cAMP in response to vasopressin and the net decrease in cAMP in response to parathyroid hormone are the result of these differential effects and are consistent with the physiological effects of chlorpropamide in vivo.