Copyright © 1988 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. Norepinephrine Infusions Increase Adenylate Cyclase

Previous work from our laboratory demonstrated that exposing adapted rats whose IBAT had been denervated surgically. lnfu-rats to cold increases interscapular brown adipose tissue (IBAT) sions of isoproterenol increased adenylate cyclase responsive-adenylate cyclase activity through a postreceptor modification of ness more potently than norepinephnne; however, the maximal the adenylate cyclase system. The cold-induced sensitization is effect achieved by isoproterenol was less than that produced by correlated with an increase in the activity of the sympathetic norepinephnne. Infusions of phenylephnne and clonidine had no innervation of IBAT, and is prevented by prior surgical denerva- effect on adenylate cyclase responsiveness. The effects of low tion of this tissue. The present experiments were aimed at doses of isoproterenol, however, were greatly potentiated by identifying the neurogenic signal that mediates cold-induced coinfusion of phenylephnne. Furthermore, the sensitizing effects sensitization. We found that, like cold exposure, infusions of of norepinephrine could be blocked by either propranolol or norepinephnne increased adenylate cyclase activity and en- prazosin, indicating that the effects of norepinephnne require hanced the ability of cholera toxin to ADP-nbosylate the simultaneous stimulation of beta and alpha-i adrenergic recep-stimulatory regulatory protein of adenylate cyclase (G5) in warm- tors. Exposure of many sympathetically innervated tissues to ad- In the experiments described below, we have sought to identify renergic agonists often leads to a diminished responsiveness of the neural signal as well as the receptors through which it act