The alpha-adrenoceptors that mediate contractions in strips of splenic artery from the pig were characterized by the use of selective agonists and subtype-selective antagonists. Noradrenaline, the alpha(1)-selective agonist phenylephrine and the alpha(1)-/alpha(2)-agonist oxymetazoline caused the preparations to contract with potency (pD(2)) values of 6.94, 6.14 and 7.27, respectively. Compared to noradrenaline: phenylephrine and oxymetazoline induced 93% and 78% of noradrenaline maximum effect. Conversely, the two alpha(2)-selective agonists clonidine and B-HT 920 induced only 31% and 13% of noradrenaline maximum effect. B-HT 920 only marginally contracted the tissue even when it was precontracted with phenylephrine. The alpha(2)-selective antagonist yohimbine antagonized oxymetazoline- and phenyleprine-induced contractions with affinity (pA(2)) values (6.80 and 6.74, respectively) consistent with alpha(1)-adrenoceptor interaction. This suggests that the pig splenic artery possesses only functional alpha(1)-adrenoceptors. The alpha(1)-adrenoceptor antagonists of varying subtype selectivities like WB-4101, 5-methylurapidil, benoxathian and BMY 7378 competitively antagonized phenylephrine-induced contractions with affinity values of 9.46, 8.26, 9.06 and 6.91, respectively. These values correlated highly with published affinity values for functional alpha(1A)-adrenoceptors (r=0.92) and alpha(1a)-clones (r=0.94) and less well with affinity values for functional alpha(1B)-adrenoceptors (r=0.84) and alpha(1b)-clones (r=0.87). Conversely, correlation with functional alpha(1D)-adrenoceplors (r=0.26) and alpha(1d)-clones (r=0.33) was poor. In addition the alpha(1D)-selective antagonist BMY 7378 had a low affinity value compared to that reported for alpha(1D)-adrenoceptors. Therefore, based on correlation studies, the plot that resembled the line of equal values most closely was that for the alpha(1A)-subtype. The alpha(1A)-selective antagonist RS-17053 antagonized phenylephrine-induced contractions in an apparently non-competitive manner and gave an apparent pA(2) value of 7.06 which is similar to the "low" affinity values reported in other alpha(1A)-containing tissues. Exposure to the irreversible alpha(1B/D)-antagonist chloroethylclonidine slightly decreased maximum response to phenylephrine without significantly affecting its potency value, indicating that the phenylephrine response is substantially chloroethylclonidine-insensitive. It is concluded that splenic artery ships from the pig contract in response to phenylephrine through activation of alpha(1)-adrenoceptors which display the pharmacological profile of the alpha(1A)-subtype for which the recently reported alpha(1A)-selective antagonist RS-17053 shows low affinity. Evidence for contribution of the alpha(1B)-subtype in the overall contractile response is elusive while no evidence was obtained for the involvement of the alpha(1D)-subtype. The contribution of functional alpha(2)-adrenocepcors to the contractile response was ruled out.
