Calcium Antagonists and Lipolysis in Isolated Rat Epididymal Adipocytes: Effects of Tetracaine, Manganese, Cobaltous and Lanthanum Ions and D600

Abstract

The present study reports the effects on lipolysis occurring in isolated rat epididymal adipocytes of several agents which have each been found to interfere with membrane calcium transport in a variety of tissues. As reported by other workers, the local anesthetic tetracaine was a strong inhibitor of hormone accelerated but not of basal lipolysis. The bivalent cations Mn²⁺ and Co²⁺ were similarly found to inhibit lipolysis stimulated with either epinephrine, ACTH, theophylline or dibutyryl cyclic AMP, whereas basal lipolysis was not markedly altered. This effect of Mn²⁺ and Co²⁺ was not mimicked by either Sr²⁺, Ba²⁺, Mg²⁺ or Ca²⁺. Cyclic AMP levels in adipocytes stimulated with epinephrine or ACTH tended to be higher in the presence of Mn²⁺ and Co²⁺. It is concluded, therefore, that Mn²⁺ and Co²⁺ inhibit lipolysis by uncoupling cyclic AMP accumulation from activation of triglyceride lipase. In contrast to Mn²⁺ and Co²⁺, the calcium antagonists La³⁺ and D600 were without effect on lipolysis. The antilipolytic effect of tetracaine, Mn²⁺ and Co²⁺ was found to persist in the absence of extracellular calcium, suggesting therefore that the antilipolytic effect of these drugs is unrelated to inhibition of calcium influx into adipocytes. The possibility is discussed that lipolytic agents cause an intracellular redistribution of calcium ion and that local anesthetics, Mn²⁺ and Co²⁺ interfere with lipolysis by preventing this intracellular redistribution of calcium.

Key words

Adipose Tissue - Lipolysis - Calcium - Cyclic AMP