Effects of Protein Kinase C Modulation on Hepatic Hemodynamics and Glucoregulation

• Published in: The Korean journal of physiology & pharmacology Vol. 3; no. 6; pp. 571 - 578
• Main Authors: Lee, Joong-Woo, Kong, In-Deok, Park, Kyu-Sang, Chung, Hae-Sook, Filkins, James P
• Format: Journal Article
• Language: Korean
• Published: 대한생리학회-대한약리학회 01.01.1999; The Korean Journal of Physiology & Pharmacology Editorial Office
• Subjects: Protal vein; Protein kinase C; Perfused liver; Glucose output; Hepatocyte; PMA
• ISSN: 1226-4512; 2093-3827

This study evaluated the effects of PKC activation using phorbol 12-myristate 13-acetate (PMA) and PKC inhibition using the isoquinoline sulfomide derivative H-7 on hemodynamics and glucoregulation in the isolated perfused rat liver. Livers were isolated from fed male Holtzman rats and perfused with Krebs Ringer bicarbonate solution under a constant flow of 50 ml/min at $35^{\circ}C.$ Portal vein pressure, glucose and lactate concentrations in the medium and oxygen consumption rates were continuously monitored by a Grass polygraph, YSI glucose and lactate monitors, and a YSI oxygen monitor, respectively. PMA at concentration of 2 to 200 nM increased the portal vein pressure, glucose and lactate production, but decreased oxygen consumption rate in a dose-dependent fashion. H-7 $(200\;{\mu}M)$ attenuated PMA (50 nM)-induced vasoconstriction $(15.1{\pm}1.36\;vs\;10.56{\pm}1.17\;mmHg),$ glucose production rate $(91.3{\pm}6.15\;vs\;71.8{\pm}2.50\;{\mu}moles/g/hr),$ lactate production rate $(72.4{\pm}6.82\;vs\;53.6{\pm}4.82\;{\mu}moles/g/hr)$ and oxygen consumption rate $(33.7{\pm}1.41\;vs\;27.9{\pm}1.75\;{\mu}l/g/min).$ The effects of PMA were blocked either by addition of verapamil $(9\;{\mu}M)$ or perfusion with $Ca^{2+}-free$ KRB. These results suggest that the hemodynamic and glucoregulatory changes in the perfused rat liver are mediated by protein kinase C activation and require $Ca^{2+}$ influx from the extracellular fluid.