Functional evidence for an alpha sub(1B)-adrenoceptor mediating contraction of the mouse spleen

alpha sub(1)-Adrenoceptor agonists ((-)-adrenaline = (-)-noradrenaline >> 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 x 10 super(-6)-6 x 10 super(-5) M) and partially attenuated by SZL-49 (10 super(-7)-10 super(-6) M), but remained resistant to ( plus or minus )-isradipine (10 super(-9)-10 super(-7) M). The contractions were competitively antagonized by low concentrations of the alpha sub(1B)-adrenoceptor-selective antagonist, spiperone (pA sub(2) = 8.29), but by relatively high concentrations of the alpha sub(1A)-adrenoceptor-selective receptor antagonists, tamsulosin (pA sub(2) = 8.62), 5-methyl-urapidil (pA sub(2) = 7.03), (+)-niguldipine (pA sub(2) = 6.26) and the alpha sub(1D)-adrenoceptor-selective antagonist, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro-[4.5]decane-7,9-dione (BMY 7378) (pA sub(2) = 6.76). Functional antagonist affinities at mouse spleen alpha sub(1)-adrenoceptors were consistent with those at guinea-pig splenic alpha sub(1B)-adrenoceptors, but not with those of either rat vas deferens alpha sub(1A)- or rat aortic alpha sub(1D)-adrenoceptors. Antagonist affinities at mouse spleen alpha sub(1)-adrenoceptors correlated also best with published antagonist data on cloned and expressed alpha sub(1b)-adrenoceptors but less well with those for either alpha sub(1a)- or alpha sub(1d)-adrenoceptors. The results provide pharmacological evidence that the alpha sub(1)-adrenoceptor mediating smooth muscle contraction of mouse spleen is the B subtype.