Effects of alamethicin on hormonal activation of renal adenylate cyclase

Abstract

The effects of the peptide antibiotic, alamethicin, on hormonally stimulated adenylate cyclase were studied in the rat kidney. In the medullary 100,000 g fraction, antidiuretic hormone-stimulated adenylate cyclase activity was observed only in the presence of alamethicin. Alamethicin augmented the stimulatory effect of parathyroid hormone in the cortical 100,000 g fraction. Lubrol PX solubilized adenylate cyclase activity but, in contrast to alamethicin, did not increase PTH stimulation of adenylate cyclase. Alamethicin had little effect in 1,000 g fractions. Therefore, the effects of this antibiotic do not appear to be due to direct stimulation of adenylate cyclase. In addition, the results cannot be explained by inhibition of phosphodiesterase by alamethicin. Alamethicin is known to increase ionic conductance in membranes by the formation of channels. The effects of alamethicin on adenylate cyclase in the 100,000 g fraction could be due to the formation of channels which increase the permeability of vesicles and thereby increase accessibility to substrate and/or hormones. Different physiochemical properties of renal cortical and medullary plasma membranes are suggested by differences observed in the responsiveness of adenylate cyclase to hormones and to alamethicin. The presence of latent antidiuretic hormone-stimulated adenylate cyclase was observed in the outer medullary 100,000 g fraction.