Interaction between α_1B - and other α₁ - and α₂ -adrenoceptors in producing contractions of mouse spleen

We have investigated the interaction of α₁ - and α₂ -adrenoceptor subtypes in producing isometric contractions to NA in mouse whole spleen. The α₁ -adrenoceptor antagonist prazosin (10^-8  M) or the α₂ -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 α_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 α_1A/D -KO mice, in which the only α₁ -adrenoceptor present is the α_1B -adrenoceptor, prazosin still antagonized contractions to NA. The α_1A -adrenoceptor antagonist RS100329 (3 × 10^-9  M) produced significant shifts in the effects of higher concentrations of NA (EC₅₀ and EC₇₅ levels) and the α_1D -adrenoceptor antagonist BMY7378 (3 × 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 α_1D -adrenoceptor and α_1A -adrenoceptor components and suggest that the α_1B -adrenoceptor interacts with an α_1D -adrenoceptor, and to a lesser extent an α_1A -adrenoceptor, at low, and an α_1A -adrenoceptor at high, NA concentrations. This study demonstrates the complex interaction between α₁ - and α₂ -adrenoceptor subtypes in producing contractions of mouse spleen and may have general implications for α-adrenoceptor mediated control of smooth muscle.