Pharmacological property of tributyltin in vivo and in vitro.
Tributyltin (TBT), an assumed endocrine-disrupting chemical, is widely known to show harmful effects in invertebrates including the dioecious snails. As for mammals, there are several reports concerning TBT toxicology, but few indications about general pharmacology of TBT. In the present study, we comprehensively examined the pharmacological effects of TBT both in vivo and in vitro. TBT (0.3 or 1.0 mg/kg) attenuated the small intestinal propulsive activity measured by the charcoal method in vivo, and caused concentration-dependent relaxation of isolated guinea-pig ileum in vitro (1.0x10(-8)-3.0x10(-6) M). TBT induced concentration-dependent relaxation of guinea-pig trachea, which was not inhibited by pre-treatment with a beta-adrenoceptor antagonist. TBT caused a concentration-dependent contraction of rat aortae, and also evoked endothelium-dependent relaxation in the presence of an alpha-adrenoceptor antagonist. The relaxation was inhibited by a muscarinic receptor antagonist. TBT reduced the electrically evoked, sympathetic contractile responses of rat vas deferens, which were slightly prevented by an alpha(2)-adrenoceptor antagonist. These results suggest that TBT possesses diverse pharmacological properties in mammalian organs.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan
S
Mizuhashi
Y
Ikegaya
N
Matsuki