Interaction between alpha(1B)- and other alpha(1)- and alpha(2)-adrenoceptors in producing contractions of mouse spleen mouse spleen alpha(1)-adrenoceptors

We have investigated the interaction of alpha(1)- and alpha(2)-adrenoceptor subtypes in producing isometric contractions to NA in mouse whole spleen. The alpha(1)-adrenoceptor antagonist prazosin (10(-8) M) or the alpha(2)-adrenoceptor antagonist yohimbine (10(-6) M) alone produced only small shifts in NA potency in wild type (WT) mice, but the combination produced a large shift in NA potency. In spleen from alpha(1A/D)-KO mice, the effects of prazosin and the combination of prazosin and yohimbine were similar to their effects in WT mice. Hence, in alpha(1A/D)-KO mice, in which the only alpha(1)-adrenoceptor present is the alpha(1B)-adrenoceptor, prazosin still antagonized contractions to NA. The alpha(1A)-adrenoceptor antagonist RS100329 (3 x 10(-9) M) produced significant shifts in the effects of higher concentrations of NA (EC50 and EC75 levels) and the alpha(1D)-adrenoceptor antagonist BMY7378 (3 x 10(-8) M) produced significant shifts in the effects of lower concentrations of NA (EC25 and EC50 levels). The effects of BMY7378 and RS00329 demonstrate alpha(1D)-adrenoceptor and alpha(1A)-adrenoceptor components and suggest that the alpha(1B)-adrenoceptor interacts with an alpha(1D)-adrenoceptor, and to a lesser extent an alpha(1A)-adrenoceptor, at low, and an alpha(1A)-adrenoceptor at high, NA concentrations. This study demonstrates the complex interaction between alpha(1)- and alpha(2)-adrenoceptor subtypes in producing contractions of mouse spleen and may have general implications for alpha-adrenoceptor mediated control of smooth muscle.