[Effect of chlorpromazine on K+-dependent regulation of aldosterone biosynthesis in guinea pig adrenal cortex].
The effects of chlorpromazine, a calmodulin inhibitor, on K(+)-dependent regulation of aldosterone biosynthesis were studied in sections and dispersed adrenocortical cells of guinea pigs. K ions in concentrations 5-11 mM significantly (p < 0.01) stimulated aldosterone and protein biosynthesis and protein phosphorylation in sections and cells of the guinea pig adrenal cortex. Using the radioautography of P-labeled polypeptides separated in polyacrylamide gel, the authors have demonstrated K+ enhancement of phosphate incorporation in the proteins with molecular masses of 40 and 75 kD in the cytosols and of 75 kD proteins in the mitochondria. Chlorpromazine in concentration 50 microM reduced K(+)-stimulated steroidogenesis and protein phosphorylation, simultaneously increasing labeled phosphate incorporation in the proteins in low K+ concentrations, not stimulating steroidogenesis. K(+)-stimulated protein biosynthesis was virtually unchanged in the presence of chlorpromazine. Increased K+ concentration in the medium resulted in reduction of cGMP concentration in adrenal cortex sections. The nucleotide level grew in the presence of chlorpromazine in elevated concentrations of K+ and reduced if the ion concentrations were low (1-3 mM). The mechanisms of chlorpromazine effect on K(+)-dependent steroidogenesis changes, protein phosphorylation and cGMP levels in the adrenocortical tissue are discussed, as is the role of calmodulin in K(+)-dependent regulation of aldosterone biosynthesis.
Pushkarev
V M
VM
Tron'ko
N D
ND
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002746:Chlorpromazine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010766:Phosphorylation; D011188:Potassium / Q000502:physiology*; D014176:Protein Biosynthesis
D002147:Calmodulin; D000450:Aldosterone; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium; D002746:Chlorpromazine
Vliianie khlorpromazina na K+-zavisimuiu reguliatsiiu biosinteza al'dosterona v kore nadpochechnikov morskikh svinok.