Abstract
Furosemide has been reported to have a suppressive effect on ADH-, PTHand adrenaline-stimulated adenosine 3':5'-cyclic monophosphate (cAMP) production, but the effect on adrenocorticotropin (ACTH) action has not yet been elucidated. In the present study, therefore, the effects of furosemide on cAMP and also on guanosine 3':5'-cyclic monophosphate (cGMP) and corticosterone, stimulated by ACTH in monolayer cultured rat adrenal cells, were investigated.
The intra-and extracellular cAMP stimulated by ACTH was dose-dependently suppressed by furosemide within the concentration range of 10-3M to 3×10-3M, and the suppressive effect of the drug was accompanied with decreased corticosterone production. However, non-stimulated basal corticosterone production was not influenced by the drug even at 3×10-3M. A similar suppressive effect of dibutyryl cAMP-stimulated corticosterone production by 3×10-3M furosemide was observed. The intracellular cAMP bound to its binding protein in sonicated adrenal cell extract was also suppressed in a very similar dose-dependent manner to total cAMP. However, though the effect on corticosterone production was also observed when the calcium concentration in the loading medium was changed, the magnitude of the effectiveness (percent of control) was relatively constant at each calcium concentration, suggesting that furosemide may not affect the site (s) at which calcium acts. Intracellular cGMP, on the other hand, was increased by 10-3 M to 3×10-3 M of furosemide, suggesting an intensifying effect of furosemide on guanylate cyclase activity. Dibutyryl cGMP-stimulated corticosterone production was also increased at the same concentration range.
These results indicated that furosemide may act not only on adenylate cyclase but also on the additional step (s) to suppress the resultant corticosterone production. In contrast to the effects of furosemide on such cAMPmediated processes, this drug treatment appeared to enhance cGMP-mediated corticosterone production.
