[Stimulated corticosterone production by alpha-human atrial natriuretic polypeptide with increased cyclic GMP...

Several studies on the effects of atrial natriuretic polypeptide (ANP) on aldosterone production using isolated adrenal cells have been reported, and they have consistently demonstrated the reduced production of aldosterone by ANP. However, the results on the corticosterone production are sundry. Since ANP selectively activates particulate guanylate cyclase, a possibility could exist that cyclic GMP is the second messenger of ANP signal transduction. In order to demonstrate unequivocally a correlation of cyclic nucleotide levels with the ANP-induced steroidogenesis, we investigated the effects of various concentrations of alpha-human atrial natriuretic polypeptide (alpha-hANP) on aldosterone, corticosterone, cyclic AMP and cyclic GMP production in isolated glomerulosa and fasciculata cells of the rats. Rat glomerulosa and fasciculata cells were obtained by enzymatic digestion of the adrenals of male Wistar rats. The cell pellet was suspended in Hanks balanced salt solution-0.1% BSA buffer and distributed in 900 microliter aliquots to 12 X 75 mm glass tubes. The samples were preincubated for 90 min. in a 37 degrees C water bath under an atmosphere of 5% CO2/95% O2. Aliquots of the test samples were added in a 100 microliter volume and incubated for 4 hr. Total volume of the incubation mixture is 1.0 ml. Aldosterone, cyclic AMP and cyclic GMP were measured by radioimmunoassay and corticosterone was determined by fluorimetric method. The results indicated that alpha-hANP inhibited the secretion of aldosterone and corticosterone in rat glomerulosa cells. Alpha-hANP significantly decreased cyclic AMP production in the rat glomerulosa cells, while it markedly stimulated cyclic GMP production.(ABSTRACT TRUNCATED AT 250 WORDS)