Both α1B- and α1A-adrenoceptor subtypes are involved in contractions of rat spleen.

Abstract

The spleen is a reservoir for circulating blood cells, and can contract to expel them. We have investigated the adrenoceptors involved in isometric contractions of rat spleen produced by noradrenaline (NA) and the α1-adrenoceptor agonist phenylephrine (Phe). Contractions to NA were antagonized by both the α1-adrenoceptor antagonist prazosin (10-8M) and the α2-adrenoceptor antagonist yohimbine (10-6M), and the combination produced further shifts in NA potency. Contractions to Phe were antagonized by prazosin (10-8M) which caused a marked parallel shift in the concentration-response curve. High non-selective concentrations of the α1D-adrenoceptor antagonist BMY7378 (10-6M), the α1A-adrenoceptor antagonist RS100329 ((3×10-8M), and the putative α1B-adrenoceptor antagonist cyclazosin (10-8M) also produced parallel shifts in the Phe concentration-response curve. BMY7378 at the selective concentration of 3×10-8M had no effect on responses to Phe, but RS100329 in the selective concentration of 3×10-9M produced a marked shift in the effects of high concentrations of Phe. Hence, antagonists in concentrations that block both α1A- and α1B-adrenoceptors produce approximately parallel shifts in Phe potency. Contractions of rat spleen to adrenergic agonists involve α2- and α1B-adrenoceptors, with a lesser role for α1A-adrenoceptors. This confirms the suggestion that smooth muscle contractions commonly involve multiple subtypes.