ALPHA(1)-ADRENOCEPTOR SUBTYPE SELECTIVITY OF TAMSULOSIN - STUDIES USING LIVERS FROM DIFFERENT SPECIES

The subtype selectivity of the alpha(1)-adrenoceptor antagonist, tamsu losin, was tested using hepatocytes and liver membranes from guinea pi gs and rabbits (expressing alpha(1)-adrenoceptors with alpha(1A) pharm acology) and rats (alpha(1B)-adrenoceptors). Tamsulosin blocked the al pha(1)-adrenergic activation of phosphorylase with higher affinity in hepatocytes from guinea pigs and rabbits than in those from rats. [H-3 ]Tamsulosin binding to liver membranes was rapid, reversible and satur able. The K-d values obtained also indicated higher affinity for alpha (1A)-adrenoceptors (70 and 140 pM, for liver membranes obtained from g uinea pigs and rabbits, respectively) than for those of the alpha(1B)- subtype (510 pM). Chloroethylclonidine potently and completely inactiv ated [H-3]tamsulosin binding sites in membranes from rabbit and rat li vers, but not those in guinea pig liver membranes. Binding competition and inactivation experiments were performed to further characterize t he receptor subtypes present in the livers of these animals. In summar y, tamsulosin is a very potent alpha,-adrenoceptor antagonist that has higher affinity for alpha(1A) -adrenoceptors than for those of the al pha(1B)-subtype.