Characterization of the alpha 1-adrenoceptor subtype mediating contraction of guinea-pig spleen.

A series of alpha 1-adrenoceptor agonists evoked concentration-dependent contraction of isolated guinea-pig spleen strips ((-)-adrenaline > (-)-noradrenaline >> L-phenylephrine > (-)-(4aR, 10aR)-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), whereas indanidine, methoxamine, oxymetazoline and UK-14.304 were ineffective. (-)-Noradrenaline-induced contractions were inhibited by chloroethylclonidine (3 x 10(-6)-6 x 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 of the splenic strips were competitively antagonized by low concentrations of the alpha 1B-adrenoceptor-selective antagonist, spiperone (pA2 8.05), but by relatively high concentrations of the alpha 1A-adrenoceptor-selective antagonists, (+)-niguldipine (pA2 6.32) and 5-methyl-urapidil (pA2 6.95). The affinities of subtype-selective antagonists determined at guinea-pig spleen alpha-adrenoceptors significantly correlated with pKi values at rat liver alpha 1B binding sites (r = 0.96) and pA2 values at putative alpha 1B-adrenoceptors in rat aorta (r = 0.95), but differed from pKi values at rat cortical alpha 1A binding sites and pA2 values at alpha 1A-adrenoceptors in rat vas deferens. Also no correlation was obtained between antagonist affinities at guinea-pig spleen alpha-adrenoceptors and alpha 1C binding sites in rabbit liver. Thus, from the (1) potencies of agonists, (2) affinities of subtype-selective antagonists and (3) differential sensitivity of the contractions to alpha 1-adrenoceptor inactivating agents and their resistance to Ca2+ channel blockade, the alpha 1-adrenoceptor mediating smooth muscle contraction of guinea-pig spleen can be best characterized as being of the B subtype.