Effects of Protein Kinase C Modulation on Hepatic Hemodynamics and Glucoregulation
Effects of Protein Kinase C Modulation on Hepatic Hemodynamics and Glucoregulation
- Joong Woo Lee In Deok Kong Kyu Sang Park Hae Sook Chung James P Filkins
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제3권 제6호
- 등재여부 : KCI등재
- 1999.01
- 571 - 578 (8 pages)
<P> 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<SUP>o</SUP>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 (200μM) attenuated PMA (50 nM)- induced vasoconstriction (15.1⁑1.36 vs 10.56⁑1.17 mmHg), glucose production rate (91.3⁑6.15 vs 71.8⁑2.50μmoles/g/hr), lactate production rate (72.4⁑6.82 vs 53.6⁑4.82μmoles/g/hr) and oxygen consumption rate (33.7⁑1.41 vs 27.9⁑1.75μl/g/min). The effects of PMA were blocked either by addition of verapamil (9μM) or perfusion with Ca<SUP>2⁢</SUP>-free KRB. <P> These results suggest that the hemodynamic and glucoregulatory changes in the perfused rat liver are mediated by protein kinase C activation and require Ca<SUP>2⁢</SUP> influx from the extracellular fluid.