Adenyl Cyclase in Fat Cells

Abstract

Abstract The similarity in the chemical structures of secretin and glucagon prompted an investigation of the comparative effects of these hormones on adenyl cyclase activity in ghosts of rat fat cells and in a preparation of purified plasma membranes from rat liver. Secretin did not activate adenyl cyclase or inhibit the stimulatory effects of glucagon on an adenyl cyclase system in plasma membranes of rat liver. Secretin and glucagon stimulated adenyl cyclase activity in ghosts of fat cells. Secretin was a more potent stimulator of the enzyme; concentrations of secretin and glucagon giving half-maximal activities were, respectively, 0.1 and 0.3 µg per ml, and maximal activity given by secretin was about twice that given by glucagon. Secretin was also more effective than glucagon in stimulating lipolysis in isolated fat cells. Combination of secretin and glucagon at maximal concentrations (20 µg per ml) did not give additive adenyl cyclase activities in ghosts, indicating that the hormones activate the same enzyme system in fat cells. Ethylene glycol bis(β-aminoethyl ether)-N,N'-tetraacetic acid, a chelator of calcium, abolished the effects of adrenocorticotropin (ACTH) on adenyl cyclase in ghosts but did not inhibit the effects of secretin, glucagon, thyroid-stimulating hormone, and luteinizing hormones. 1-(2,4-Dichlorophenyl)-1-hydroxy-2-t-butylamino)ethane hydrochloride, a β-adrenergic agent, stimulated adenyl cyclase and inhibited the effects of epinephrine. DCB did not inhibit the effects of secretin, glucagon, and ACTH. Pretreatment of adipose tissue with trypsin decreased by 44% the lipolytic response of isolated fat cells to glucagon, but it had no effect on their response to secretin and ACTH. Glucagon did not stimulate adenyl cyclase activity in ghosts prepared from trypsin-treated fat cells; the effects of secretin and ACTH on the enzyme were reduced by 60 and 40%, respectively. Trypsin treatment had no effect on the activation of adenyl cyclase by fluoride ion and epinephrine. It is concluded that secretin activates adenyl cyclase in fat cells via a receptor that is distinct from the receptors for glucagon and the other lipolytic hormones. It is suggested that the receptors for the peptide hormones are protein in character and are localized on the outer surface of the plasma membrane of fat cells.