Endogenous carbon monoxide suppression stimulates bile acid
-dependent biliary transport in perfused rat liver.
Sano, Tsuyoshi, Masaya Shiomi, Yoshiyuki Wakabayashi, Yuichi Shinoda,
Nobuhito Goda, Tokio Yamaguchi, Yuji Nimura, Yuzuru Ishimura, and
Makoto Suematsu.
Department of Biochemistry, School of Medicine, Keio University,
Tokyo 160, First Department of Surgery, School of Medicine, Nagoya
University, Nagoya 466, Department of Biochemical Genetics, Medical
Research Institute
APStracts 3:0258G, 1996.
This study aimed to investigate whether CO, a product of heme
oxygenase which degrades protoheme IX, serves as an endogenous
modulator for biliary transport. To that end, effects of zinc
protoporphyrin IX (ZnPP), a heme oxygenase inhibitor, on the biliary
transport were tested in perfused rat liver. Perfusion of 1 [mu]M
ZnPP abolished detectable levels of CO in the venous perfusate and
increased bile acid-dependent bile output accompanying an increased
secretion of bile salts. The ZnPP-induced choleresis coincided with a
reduction of tissue cGMP levels and a decrease in vascular
conductance. Upon administration of 2.5 [mu]M CO, the ZnPP-elicited
choleresis, the decreases in vascular conductance and cGMP levels
were all attenuated. Treatment with 1[mu]M 8Br-cGMP partly attenuated
the ZnPP-induced choleresis in concert with repression of vascular
conductance. Furthermore, treatment of the liver with methylene blue,
a guanylate cyclase inhibitor, evoked a choleresis similar to that
induced by ZnPP. Thus, endogenous CO suppression stimulates the
biliary transport, in part, through a cGMP-dependent mechanism.
Received 11 July 1996; accepted in final form 14 November 1996.
APS Manuscript Number G276-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996