Effect of ionophorous antibiotics (nigericin, gramicidin and valinomycin) on cyclic AMP synthesis in rat adipose tissue

Abstract

The antibiotic nigericin increases the permeability of natural and artificial membranes to hydrogen ions and promotes potassium-hydrogen exchange. It has been shown to inhibit the catecholamine-induced lipolysis in rat epididymal fat. The effect of nigericin was also tested, together with two other ionophorous antibiotics, gramicidin and valinomycin, on cyclic AMP synthesis stimulated in adipose tissue by noradrenaline and theophylline. The last two agents have previously been found to inhibit hormoneinduced lipolysis in a manner similar to that of nigericin. In contrast to their common antilipolytic activity, the three drugs had different effects on cyclic AMP synthesis. Valinomycin did not depress the increase of the cyclic nucleotide, while gramicidin and nigericin caused its inhibition. The comparison between the three drugs is interesting as they differ in cation (mainly K + and Na +) and proton specificity, whilst having a similar final metabolic effect, i.e., the discharge or reduction of mitochondrial energy. The similar effect on lipolysis, in contrast to the different action on cyclic AMP synthesis, suggests that the three ionophorous antibiotics depress or inhibit the activation of the lipolytic process by lowering the availability of ATP after the synthesis of the cyclic nucleotide.