Receptor-mediated biphasic alteration of hepatocellular transport from hepatocyte to bile canaliculi as measured by near-infrared spectroscopy: a novel test with glucagon for biliary excretion.
As glucagon is known to cause a receptor-mediated increase in intracellular calcium and cyclic AMP, we have developed a novel method of evaluating the integrity of the signal transduction and transport system using glucagon-induced changes in indocyanine green (ICG) excretion. The kinetics of the hepatocellular concentration of ICG at 4-second intervals was analyzed by near-infrared spectroscopy in vivo on the liver surface. After intravenous injection of 0.5 mg/kg ICG to rabbits, absorbance of ICG increased and then decreased according to the two-compartment model: ICG(t) = -Aexp(-alphat) + Bexp(-betat), where alpha and beta (min(-1)) indicate the time constants of uptake and excretion, respectively. During the excretion phase, 40 microg/kg glucagon was infused as a bolus via the portal vein. A biphasic acceleration and retardation of ICG excretion from the baseline exponential decay was observed in the controls. In order to perturb the glucagon response, colchicine, ouabain, wortmannin and an ischemia-reperfusion insult were employed. Colchicine, ouabain and wortmannin abolished the biphasic acceleration and retardation of ICG excretion. Glucagon response was absent upon the ischemia-reperfusion insult. The observed biphasic response to glucagon clearly indicates that glucagon modulates bile canalicular contraction and peristalsis via the two glucagon receptors and these second messengers. The glucagon response requires the integrity of signal transduction, cytoskeleton structure, myosin function, and bile canalicular pump.
Department of Surgery, Maizuru Municipal Hospital, Maizuru, Kyoto, Japan. director@hospital.maizuru.kyoto.jp
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Tanaka
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Shinohara
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Yamaoka
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004396:Coloring Agents / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism*; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007329:Insulin Antagonists / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D019265:Spectroscopy, Near-Infrared; D000077191:Wortmannin
D000730:Androstadienes; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D007329:Insulin Antagonists; D010042:Ouabain; D005934:Glucagon; D007208:Indocyanine Green; D000077191:Wortmannin