Effects of trinucleotides on hormonally responsive adenylate cyclase activity in rat kidney

Abstract

The effects of trinucleotides on basal and hormonally stimulated adenylate cyclase activity in rat kidney homogenates was evaluated. In the absence of added trinucleotides, parathyroid hormone (PTH) increased cortical adenylate cyclase activity, while antidiuretic hormone (ADH) increased medullary activity; however, prostaglandin (PG)E 2 did not stimulate adenylate cyclase activity in the renal cortex, outer medulla, or inner medulla. However, with exogenous guanosine 5′-triphosphate (GTP) at concentrations as low as 8 × 10 −7 M, PGE 2 did activate adenylate cyclase. This effect was seen over a concentration range of 8 × 10 −7 to 8 × 10 −4 M PGE 2. In addition, deoxyGTP and cytosine 5′-triphosphate (CTP) were also effective in the cortex, and deoxyGTP was effective in the inner medulla. GTP also augmented PTH stimulation slightly in the cortex, but had no effect on ADH stimulation in medullary tissue. Therefore, a diference in the GTP requirement was observed for prostaglandins compared to polypeptide hormones. When stimulation by PTH or ADH was examined over a wide concentration range, no dependency upon GTP for stimulation was observed. Furthermore, when the ATP concentration was reduced from 2 to 0.2 m M and Mg ++ concentration was varied from 1 to 5 m M, a dependency of either PTH or ADH stimulation upon GTP was still not observed. Guanylyl 5′-imidodiphosphate (8 μ M) elevated both basal and polypeptide hormone activity in all three tissues but did not elevate PGE 2 above basal values for that group. GTP appears to be important in renal regulation of PGE 2-stimulated adenylate cyclase activity.