Effects of hormones on cyclic AMP release in perfused rat livers

Abstract

The in ~itro perfusion of rat ~vers has p~oven to be a valuable tool for the investigation of the mechanism of action of g]ucagon, epinephrine aa~d insuhn on intact ~ve~ c.e~s I1-7]. The,~ effects on adenylate cyclase and ~ue concomitant changes ~ cycle AMP (adenosine 3'05'-cyclic monophosphate) p~.sduction play an important role ha the sequence of events from !he hor-~one-reeeptor interaction to ~e metabolic response .of the ~ell [1.17]. As :t has been shown that cyclic ~a~MP is released by gver ceils in ~esponse to glucagon and epS~ephfine [5, 7 10], a de~a~led study of ~he kinetic~ ,of t]~s re.arise wo~ld a~ow to correlate it more properly with ~e k~netics of subsequent rectaboric events. Reckculafion of relatively ~ma]l volume~ of perfusate through the liwer makes it impossible Io keep hormone concentrations constant and ~ay therefore blunt or ~ter hormonal effects by feed-back mechanism. Swillcligg from recilculat'mg to nonrecireulathag perfusion just befor, e the addition of homaone ~ters tile concentration of metabolites Jn ~the perfu~te before they wexe modulNed by the ha,tin,one it~lf. T~.e~e dSffJculties may be ove~c~me by the non-~,ecircutating perfuaion. With this rystern, the time course of cyclic AMP outpm by the ~ver was fellowed in the presence of h,onnonesinfluenchag adenylate cyclaze activity. ' " i" ~ -. "" ':' / ' /" " ".