Reginald W. Butcher

THE EFFECTS OF THE CATECHOLAMINES, ADRENERGIC BLOCKING AGENTS, PROSTAGLANDIN E1, AND INSULIN ON CYCLIC AMP LEVELS IN THE RAT EPIDIDYMAL FAT PAD IN VITRO*

The Role of Cyclic A M P in the Lipolytic Response of Adipose Tissue. Cyclic A M P t appears to mediate a t least in part the lipolytic actions of the catecholamines and several other lipolytic hormones in rat epididymal fat pads in ~ i t r o . ’ ~ The data which led to this conclusion may be summarized as follows: a. Exogenous cyclic AMP, or the derivative N6-2’ O-dibutyryl cyclic AMP, stimulated lipolysis when added to incubating fat pads or isolated fat cells.’-3 b. Lipolytic rates and cyclic A M P levels were compared in fat pads incubated in a variety of conditions.”’ Incubation or perfusion of fat pads with epinephrine produced increases in cyclic A M P which occurred a t least as rapidly as the increased rate of free fatty acid release. These changes in cyclic A M P were elicited by concentrations of epinephrine in the same range as those required for the lipolytic action. Caffeine (an inhibitor of the cyclic nucleotide phosphodiesterase) acted synergistically with epinephrine in stimulating cyclic A M P accumulation and lipolysis, and dichloroisoproterenol (DCI) antagonized the effects of epinephrine on both. c. Cell-free preparations of rat epididymal fat contained an epinephrinesensitive adenyl cyclase ~ y s t e m . ~ These data, taken together, indicated that the adenyl cyclase system was the adrenergic receptor for lipolysis in fat. (For a detailed discussion of the relationship of the adenyl cyclase system to adrenergic receptors, see Reference 5 . ) The effects of hormones on lipolysis are so numerous and interrelated that it seemed desirable to investigate in depth the actions of hormones and blocking agents on the adenyl cyclase system. In the recently reviewed.studies characterizing the lipolytic receptor of fat, the effects of the adipokinetic hormones and blocking agents on lipolysis (FFA or glycerol release) have been Unfortunately, the nature and the number of steps between increased intracellular cyclic A M P and increased lipolysis are not completely