KMID : 0811719990030060571
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Korean Journal of Physiology & Pharmacology 1999 Volume.3 No. 6 p.571 ~ p.578
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Effects of Protein Kinase C Modulation on Hepatic Hemodynamics and Glucoregulation
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Joong Woo Lee
In Deok Kong/Kyu Sang Park/Hae Sook Chung/James P Filkins/Joong Woo Lee/In Deok Kong
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Abstract
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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?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¥ìM) attenuated PMA (50 nM)-induced vasoconstriction (15.1¡¾1.36vs10.56¡¾1.17mmHg), glucose production rate (91.3¡¾6.15vs71.8¡¾2.50¥ìmoles/g/hr), lactate production rate (72.4¡¾6.82vs53.6¡¾4.82¥ìmoles/g/hr) and oxygen consumption rate (33.7¡¾1.41vs27.9¡¾1.75¥ìl/g/min). The effects of PMA were blocked either by addition of verapamil (9¥ìM) or perfusion with Ca2+?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 Ca2+ influx from the extracellular fluid.
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KEYWORD
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Protein kinase C, PMA, Perfused liver, Glucose output, Protal vein, Hepatocyte,
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