TY - JOUR
T1 - Metabolic effects and cyclic AMP levels produced by glucagon, (1-Nα-trinitrophenylhistidine,12-homoarginine)glucagon and forskolin in isolated rat hepatocytes
AU - Corvera, Silvia
AU - Huerta-Bahena, Judith
AU - Pelton, John T.
AU - Hruby, Victor J.
AU - Trivedi, Dev
AU - García-Sáinz, J. Adolfo
N1 - Funding Information:
This work was supported in part by a grant from the U.S. Public Health Service AM 21085, and by a grant from CONACyT (PCCBBNA 020747). The authors thank Ms. Guadalupe Ramirez for typing the manuscript.
PY - 1984/8/17
Y1 - 1984/8/17
N2 - [1-Nα-Trinitrophenylhistidine,12-homoarginine]glucagon (THG) is a potent antagonist of the effects of glucagon on liver membrane adenylate cyclase. In isolated hepatocytes, this glucagon analogue was an extremely weak partial agonist for cAMP accumulation, and it blocked the stimulation of cAMP accumulation produced by glucagon. However, THG was a full agonist for the stimulation of glycogenolysis, gluconeogenesis and urea synthesis in rat hepatocytes, and did not antagonize the metabolic effects of glucagon under most of the conditions examined. Forskolin potentiated the stimulation of cAMP accumulation produced by glucagon or THG, but did not potentiate their metabolic actions. A much larger increase in cAMP levels seemed to be required for the stimulation of hepatocyte metabolism by forskolin than by glucagon or THG. This may suggest the existence of a functional compartmentation of cAMP in rat hepatocytes. The possible existence of compartments in cAMP-mediated hormone actions and the involvement of factors, besides cAMP, in mediating the effects of THG and glucagon is suggested.
AB - [1-Nα-Trinitrophenylhistidine,12-homoarginine]glucagon (THG) is a potent antagonist of the effects of glucagon on liver membrane adenylate cyclase. In isolated hepatocytes, this glucagon analogue was an extremely weak partial agonist for cAMP accumulation, and it blocked the stimulation of cAMP accumulation produced by glucagon. However, THG was a full agonist for the stimulation of glycogenolysis, gluconeogenesis and urea synthesis in rat hepatocytes, and did not antagonize the metabolic effects of glucagon under most of the conditions examined. Forskolin potentiated the stimulation of cAMP accumulation produced by glucagon or THG, but did not potentiate their metabolic actions. A much larger increase in cAMP levels seemed to be required for the stimulation of hepatocyte metabolism by forskolin than by glucagon or THG. This may suggest the existence of a functional compartmentation of cAMP in rat hepatocytes. The possible existence of compartments in cAMP-mediated hormone actions and the involvement of factors, besides cAMP, in mediating the effects of THG and glucagon is suggested.
KW - (Rat hepatocyte)
KW - Forskolin
KW - Glucagon
KW - Glucagon analog
KW - cyclic AMP
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U2 - 10.1016/0167-4889(84)90071-5
DO - 10.1016/0167-4889(84)90071-5
M3 - Article
C2 - 6087925
AN - SCOPUS:0021135757
SN - 0167-4889
VL - 804
SP - 434
EP - 441
JO - BBA - Molecular Cell Research
JF - BBA - Molecular Cell Research
IS - 4
ER -