Dose-response curves for the adipokinetic action of aromatic amines and adrenocorticotropin upon the isolated adipose tissue of the hamster

Abstract

Slices of hamster adipose tissue were incubated with various concentrations of an aromatic amine or of adrenocorticotropin (ACTH). The curve relating response (measured in terms of FFA produced) to logarithm of dose was sigmoid for all adipokinetic substances tested. The basic requirement for adipokinetic activity was found to be a phenyl group attached to an ethyl- or propylamine side chain. Structural features incompatible with adipokinetic activity are described. Three groups of sigmoid log dose-response curves were distinguished, characteristic of (a) ACTH, and the catechol amines norepinephrine, epinephrine, isoproterenol, ethylnorepinephrine, and 3,4-dihydroxy-α(isopropylamino)-acetophenone; (b) dichloroisoproterenol; and (c) nine aromatic amines related in structure to phenylethylamine, but lacking the combination of a catechol ring and a hydroxy or keto group on the Β-carbon. A modification of the Clark-Stetten model of hormone action is presented. Dose-response data for the action of aromatic amines and of ACTH upon hamster adipose tissue, and for the action of ACTH upon rabbit adipose tissue, are compatible with the equations derived from the model. Consideration of the structural features of aromatic amines, which influence certain parameters of these equations, supports the concept that the various adipokinetic peptides and the catecholamines act at the same site and by the same mechanism to stimulate lipolysis within the fat cell.