Glucagon-like peptide-1 activates the adenylyl cyclase system in rockfish enterocytes and brain membranes

Glucagon-like peptide (GLP) exerts important physiological functions in fis h liver, but extrahepatic sites of action and physiological roles have been largely ignored. We show here that GLP activates adenylyl cyclase in isola ted brain and enterocyte membranes and increases cellular cyclic adenosine monophosphate (cAMP) levels in isolated enterocytes of rockfish (Sebastes c aurinus). Following exposure to synthetic zebrafish GLP (zf-GLP) (1 nM-1 mu M), a concentration-dependent increase in enterocyte cAMP is noted. The ma ximum increase in cAMP levels is observed at I mu M zf-GLP, and represents a 30% increase above control values. Exendin-4, a GLP receptor agonist in m ammals, elicits a similar concentration-dependent increase in enterocyte cA MP. In contrast, norepinephrine or prostaglandin E-2 (at 1 mu M) increased cAMP levels by 2 and 4-fold, respectively. Brain membrane adenylyl cyclase is activated 20-40% by zf-GLP, and to a smaller extent by zf-glucagon, whil e exendin-4, is as effective as zf-GLP at a dose of 100 nM. These results s uggest potential physiological roles of GLP in brain and intestine in pisci ne systems analogous to GLP-1 functions in these tissues described for mamm als. (C) 1998 Published by Elsevier Science Inc. All rights reserved.