Effects of hyperosmolarity on the cyclic AMP concentration and lipolysis of the adipocyte stimulated by adrenocorticotropic hormone.

The effects of ACTH on 3',5'-cyclic AMP (cAMP) levels and lipolysis were examined on isolated adipocytes incubated in either isosmolar or hyperosmolar media. The ability of ACTH to induce intracellular cAMP accumulation was greatly enhanced by incubating cells in hyperosmolar sucrose (100 to 400 mM) solutions. Hyperosmolar solutions prepared by the addition of either NaCL, glucose or mannitol enhanced the ACTH effect on cAMP to the same extent as did the hyperosmolar sucrose solution, but hyperosmolar urea solutions did not have such an effect. The effect of hyperosmolarity was shown only in cells stimulated by lipolytic hormones, and the effects were still evident in the presence of high concentrations of theophylline, indicating the effect of hyperosmolarity is to facilitate hormone action on the receptor-coupler system of the adipocyte membrane. The action of glucagon on cAMP was augmented much less than the actions of ACTH and isoproterenol. Basal as well as ACTH or exogenous cAMP stimulated lipolysis was lower in hyperosmolar sucrose solutions. Some mechanism by which hyperosmolarity interferes with the metabolic sequence beyond the accumulation of cAMP was suggested.