Papaverine inhibits transcytotic vesicle transport and lipid excretion into bile in isolated perfused rat liver
| Autor: | James L. Boyer, Tomihiro Hayakawa, Makoto Miyaji, Tomoyuki Kumai, Takayuki Ohiwa, Tomio Nakai, James G. Corasanti, Kenji Katagiri, Makoto Hoshino, T. Takeuchi |
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| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty In Vitro Techniques Horseradish peroxidase Excretion Bile Acids and Salts Rats Sprague-Dawley chemistry.chemical_compound Cyclic nucleotide Internal medicine Papaverine medicine Animals Bile Phosphodiesterase inhibitor Horseradish Peroxidase Phospholipids Hepatology biology Cholesterol Alkaloid Biological Transport Lipid Metabolism Rats Perfusion Endocrinology chemistry Liver biology.protein Nucleotides Cyclic Peroxidase medicine.drug |
| Zdroj: | Hepatology (Baltimore, Md.). 16(4) |
| ISSN: | 0270-9139 |
| Popis: | Papaverine is a nonspecific smooth muscle relaxant and a phosphodiesterase inhibitor. Its effects on biliary excretion of lipids and horseradish peroxidase were investigated in a single-pass isolated perfused rat liver model. A constant infusion of papaverine (1.6 mumol/min; 40 mumol/L) significantly increased bile flow (microliters per minute per gram of liver) before (2.03 +/- 0.09 vs. 1.0 +/- 0.06) and after sodium taurocholate infusion (2.77 +/- 0.10 vs. 1.88 +/- 0.11). However, papaverine significantly and reversibly reduced biliary excretion of phospholipids and cholesterol (nanomoles per minute per gram of liver) after a 1.0 mumol/min sodium taurocholate infusion, from 7.45 +/- 0.83 and 1.42 +/- 0.15 to 1.75 +/- 0.18 and 0.39 +/- 0.06, respectively (p less than 0.01), whereas secretion of bile acids was unaffected. When a 1-min pulse of horseradish peroxidase (25 mg) was infused in isolated perfused rat liver after a continuous infusion of N6,O-2'-dibutyryladenosine 3',5'-cyclic monophosphate (0.25 mumol/min; 6.25 mumol/L), horseradish peroxidase appeared in bile in an early (4 to 6 min) and late (20 to 25 min) peak. Papaverine significantly reduced the late peak, from 1.211 +/- 0.264 to 0.498 +/- 0.107 (p less than 0.01). Papaverine had no significant effects on either cyclic AMP or cyclic GMP in the liver and bile, although it has been reported that papaverine is a phosphodiesterase inhibitor. These findings indicate that papaverine inhibits biliary excretion of lipids but not bile acids, and they suggest that papaverine has an inhibitory effect on transcytotic vesicle transport independent of an increase of cyclic nucleotides in hepatocytes. |
| Databáze: | OpenAIRE |
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