-(6-AMINOHEXYL)-5-CHLORO-1-NAPHTHALENESULFONAMIDE, A CALMODULIN ANTAGONIST, REVERSES THE INHIBITORY EFFECT OF INSULIN ON LIPOLYSIS DUE TO DIBUTYRYL-CYCLIC-AMP

The effects of several calmodulin antagonists on the antilipolytic act ivity of insulin were studied in isolated rat adipocytes. N-(6-aminohe xyl)-5-Chloro-1-naphthalenesulfonamide (W-7) antagonized the inhibitor y effect of insulin on lipolysis due to dibutyryl cyclic AMP (Bt2CAMP) (0.5 mM), but not due to adrenaline (1 muM) or 3-isobutyryl-1-methylx anthine (IBMX) (0.1 mM). The concentration of W-7 required for half-ma ximal suppression of antilipolytic effect of insulin (25 muU/ml) was 1 2 muM. High concentrations (up to 1000 muU/ml) of insulin could not ov ercome this suppression by W-7. W-7 did not affect the insulin binding to its receptor on fat cells. Other types of calmodulin antagonists s uch as trifluoperazine or calmidazolium did not antagonize the inhibit ory effect of insulin. These findings show that the insulin receptor o r calmodulin may not be involved in this suppressive effect of W-7.