Functional evidence for an α1B-adrenoceptor mediating contraction of the mouse spleen

Abstract

α 1-Adrenoceptor agonists ((−)-adrenaline = (−)-noradrenaline å l-phenylephrine > methoxamine > (−)-(4a R,10a R)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-methylthio-2H-naphth[2,3-b]-1,4-oxazine (SDZ NVI 085) > cirazoline) evoked contraction of isolated mouse spleen strips, whereas oxymetazoline and indanidine were nearly inactive. Splenic contractions elicited by (−)-noradrenaline were inhibited by chloroethylclonidine (3 × 10 −6–6 × 10 −5 M) and partially attenuated by SZL-49 (10 −7–10 −6 M), but remained resistant to (±)-isradipine (10 −9–10 −7 M). The contractions were competitively antagonized by low concentrations of the α 1B-adrenoceptor-selective antagonist, spiperone (pA 2 = 8.29), but by relatively high concentrations of the α 1A-adrenoceptor-selective receptor antagonists, tamsulosin (pA 2 = 8.62), 5-methyl-urapidil (pA 2 = 7.03), (+)-niguldipine (pA 2 = 6.26) and the α 1D-adrenoceptor-selective antagonist, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro-[4.5]decane-7,9-dione (BMY 7378) (pA 2 = 6.76). Functional antagonist affinities at mouse spleen α 1-adrenoceptors were consistent with those at guinea-pig splenic α 1B-adrenoceptors, but not with those of either rat vas deferens α 1A- or rat aortic α 1D-adrenoceptors. Antagonist affinities at mouse spleen α 1-adrenoceptors correlated also best with published antagonist data on cloned and expressed α 1b-adrenoceptors but less well with those for either α 1a- or α 1d-adrenoceptors. The results provide pharmacological evidence that the α 1-adrenoceptor mediating smooth muscle contraction of mouse spleen is the B subtype.