Effect of H-7 on the modulation of glucagon actions by activators of protein kinase-C.
The stimulations of ureagenesis and cyclic AMP accumulation induced by glucagon were inhibited by 10 nM vasopressin or 100 nM phorbol 12-myristate 13-acetate (PMA). The maximal accumulation of cyclic AMP induced by glucagon was clearly diminished by these agents without change in the EC50 for the peptide hormone suggesting a non-competitive type of inhibition. H-7 blocked the inhibition of glucagon-stimulated ureagenesis induced by PMA and vasopressin and diminished their effect on the accumulation of cyclic AMP induced by glucagon. It is concluded that activation of protein kinase C inhibits the stimulation of ureagenesis and the accumulation of cyclic AMP induced by glucagon in liver cells from hypothyroid rats; H-7 inhibits the effects of protein kinase C activation.
García-Sáinz
J A
JA
Instituto de Fisiología Celular, UNAM, D.F. Mexico.
Hernández-Sotomayor
S M
SM
Contreras-Rodríguez
J L
JL
Macías-Silva
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D005260:Female; D005934:Glucagon / Q000494:pharmacology*; D007037:Hypothyroidism / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014508:Urea / Q000378:metabolism
D007546:Isoquinolines; D010879:Piperazines; D001127:Arginine Vasopressin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014508:Urea; D005934:Glucagon; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate