Effects of clenbuterol on nitrogen metabolism and G6PDH activity of rat hepatocyte / 药学学报

ABSTRACT

<p><b>AIM</b>To study the effects of beta 2-adrenergic receptor-selective agonist clenbuterol on nitrogen metabolism and glucose-6-phosphate dehydrogenase activity of rat hepatocyte and its pharmacological mechanism.</p><p><b>METHODS</b>Biochemical methods were used to study the influence of clenbuterol on urea-nitrogen concentration of hepatocyte culture medium, 3H-leucine incorporation into hepatocyte, insulin-like growth factor I (IGF-I) production and glucose-6-phosphate dehydrogenase (G6PDH) activity of rat hepatocyte.</p><p><b>RESULTS</b>The results showed that urea-nitrogen production by cultured rat hepatocytes was markedly affected with clenbuterol treatment (1 x 10(-6) mol.L-1), urea-nitrogen concentration of culture medium was decreased by 25.51% (P < 0.05) compared with control. The inhibitory effect of hepatocyte urea-nitrogen production of clenbuterol was blocked by propranolol, a beta-adrenoreceptor antagonist (1 x 10(-6) mol.L-1), but hepatocyte urea-nitrogen level was not affected with propranolol treatment only (P > 0.05). The content of 3H-leucine incorporation in rat hepatocyte was significantly increased by 23.35% (P < 0.05) with clenbuterol-treatment (1 x 10(-6) mol.L-1), and the enhanced effect of 3H-leucine incorporation into hepatocyte was antagonized by propranolol (1 x 10(-6) mol.L-1. The level of 3H-leucine incorporation of rat hepatocyte was not influenced by propranolol alone. IGF-I production of rat hepatocyte might be affected by clenbuterol. IGF-I concentration of culture medium was increased by 39.46% with clenbuterol (1 x 10(-6) mol.L-1), but no significant difference was found compared with the control (P > 0.05). Moreover, G6PDH activity of rat hepatocyte was significantly decreased by 43.36% (P < 0.05) with clenbuterol treatment (1 x 10(-6) mol.L-1), and the declined effect of clenbuterol was antagonized by propranolol. G6PDH activity of rat hepatocyte was not affected on condition that propranolol was administered alone (P > 0.05).</p><p><b>CONCLUSION</b>It is suggested that clenbuterol may regulate nitrogen and fat metabolism by means of increasing nitrogen retention and protein synthesis, and decreasing G6PDH activity of rat hepatocyte for pharmacological effects.</p>