Korean J Physiol Pharmacol.
1999 Dec;3(6):571-578.
Effects of protein kinase C modulation on hepatic hemodynamics and glucoregulation
- Affiliations
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- 1Department of Physiology, Yonsei University, Wonju College of Medicine, Wonju, Korea.
- 2Department of Institute of Medical Engineering, Yonsei University, Wonju College of Medicine, Wonju 220-701, Korea.
- 3Department of Physiology, Stritch School of Medicine, Loyola university of Chicago 2160 South First Avenue Maywood, IL 60153, USA.
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 35degreeC. 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 micrometer) 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+/-2.50 micromoles/g/hr), lactate
production rate (72.4+/-6.82 vs 53.6+/-4.82 micromoles/g/hr) and oxygen
consumption rate (33.7+/-1.41 vs 27.9+/-1.75 microliter/g/min). The effects of
PMA were blocked either by addition of verapamil (9 micrometer) 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.