CHARACTERIZATION OF ADRENERGIC-RECEPTORS AND RELATED TRANSDUCTION PATHWAYS IN THE LIVER OF THE RAINBOW-TROUT

Epinephrine (EPI) is thought to act by stimulating adenylyl cyclase (A Case) and cAMP production through beta-adrenoceptors in the liver of m ore primitive vertebrates, Recent observations, however, point to an i nvolvement of alpha(1)-adrenoceptors in EPI action, at least in some f ish species, The role of the alpha(1)- and beta-adrenergic transductio n pathways has been investigated in rainbow trout (Oncorhynchus mykiss ) hepatic tissue, Radioligand-binding assays with the beta-adrenergic antagonist H-3-CGP-12177 using hepatic membranes purified on a discont inuous sucrose gradient confirmed the presence of beta-adrenoceptors ( K-d 0.36 nM, B-max 8.61 fmol . mg(-1) protein). We provide the first d emonstration of alpha(1)-adrenoceptors in these same membranes; analys is of binding data with the alpha(1)-adrenergic antagonist H-3-prazosi n demonstrated a single class of binding sites with a K-d of 15.4 nM a nd a B-max of 75.2 fmol . mg(-1) protein. There is a straight correlat ion between beta-adrenoceptor occupancy, ACase activation and cAMP pro duction. On the contrary, the role of inositol 1,4,5-trisphosphate (IP 3) has to be elucidated; in fact, despite the presence of specific mic rosomal binding sites for IP3 (K-d 6.03 nM, B-max 90.2 fmol . mg(-1) p rotein), its cytosolic concentration was not modulated by EPI. On the other hand, we have previously shown in American eel and bullhead hepa tocytes that alpha(1)-adrenergic agonists are able to increase intrace llular concentrations of IP3 and Ca2+ and to activate glycogenolysis. These data suggest a marked variation in the liver of different fish b oth in terms of alpha(1)-binding sites affinity and of alpha(1)-adreno ceptor/IP3/Ca2+ transduction systems.