Vol. 289, Issue 3, 1575-1583, June 1999

In Vivo Measurement by [³H]Tamsulosin of ₁ Adrenoceptors in Rat Tissues in Relation to the Pharmacokinetics

Shizuo Yamada, Takashi Ohkura, Yoshiharu Deguchi and Ryohei Kimura

Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

The present study was undertaken to simultaneously measure ₁ adrenoceptors in rat tissues by [³H]tamsulosin in vivo. In vivo specific [³H]tamsulosin binding was observed in the prostate, vas deferens, aorta, submaxillary gland, spleen, heart, lung, and kidney after i.v. injection of the ligand but not in the cerebral cortex and liver. Specific [³H]tamsulosin binding in the kidney, lung, heart, and spleen was greatest at 3 min after i.v. injection and declined rapidly with the disappearance of [³H]tamsulosin from the plasma. On the other hand, [³H]tamsulosin binding in the prostate and aorta peaked at 10 to 60 min after i.v. injection, and a considerable level of specific binding in both tissues persisted up to 240 min. The most sustained binding of [³H]tamsulosin occurred in the submaxillary gland. In vivo specific [³H]tamsulosin binding in rat tissues was effectively inhibited by the coinjection of low doses of unlabeled tamsulosin, prazosin, and terazosin with the radioligand but not by relatively high doses of yohimbine and propranolol. Based on estimated ID₅₀ values, in vivo inhibitory effect of tamsulosin compared with prazosin was 5 to 14 times greater in rat tissues except the spleen, which showed 1.6 times less potent than prazosin. From ratios of ID₅₀ (spleen) to ID₅₀ (submaxillary gland) or ID₅₀ (prostate), tamsulosin was 9 and 19 times, respectively, greater than prazosin in selectivity of ₁ adrenoceptors in the submaxillary gland and prostate versus the spleen, respectively, suggesting that tamsulosin binds to _1A subtype with higher affinity than _1B subtype in vivo. The present study suggests that [³H]tamsulosin is a useful radioligand for in vivo measurement of ₁ adrenoceptors in rat tissues.