Interaction between α - and other α - and α -adrenoceptors in producing contractions of mouse spleen.

We have investigated the interaction of α - and α -adrenoceptor subtypes in producing isometric contractions to NA in mouse whole spleen. The α -adrenoceptor antagonist prazosin (10  M) or the α -adrenoceptor antagonist yohimbine (10  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 α -KO mice, the effects of prazosin and the combination of prazosin and yohimbine were similar to their effects in WT mice. Hence, in α -KO mice, in which the only α -adrenoceptor present is the α -adrenoceptor, prazosin still antagonized contractions to NA. The α -adrenoceptor antagonist RS100329 (3 × 10  M) produced significant shifts in the effects of higher concentrations of NA (EC and EC levels) and the α -adrenoceptor antagonist BMY7378 (3 × 10  M) produced significant shifts in the effects of lower concentrations of NA (EC and EC levels). The effects of BMY7378 and RS00329 demonstrate α -adrenoceptor and α -adrenoceptor components and suggest that the α -adrenoceptor interacts with an α -adrenoceptor, and to a lesser extent an α -adrenoceptor, at low, and an α -adrenoceptor at high, NA concentrations. This study demonstrates the complex interaction between α - and α -adrenoceptor subtypes in producing contractions of mouse spleen and may have general implications for α-adrenoceptor mediated control of smooth muscle.