Rabbit isolated iris dilator strips were contracted by norepinephrine, an alA and aiB nonselective agonist, but not by methoxamine, an alA-selective agonist. The concentration-response curve for norepinephrine was considerably inhibited by chloroethylclonidine. The pA2 values for WB4101 and 5-methylurapidil were 8.16 ± 0.09 and 7.84 ± 0.08 (means ± S.E. of 8 -12 experiments), respectively, and significantly smaller than the values reported in the rat renal artery and thoracic aor ta, and rabbit bronchus, where the a1A-subtype is predominant. These results suggest that the rabbit iris dilator contains primarily the aiB-subtype. Clonidine and tizanidine did not contract the rabbit iris dila tor but shifted the curve for norepinephrine in a parallel manner, suggesting that they interact with the aiB-subtype and act as competitive antagonists in this muscle. Methoxamine (up to 10-3 M) had no effect on the contractile response to norepinephrine, suggesting that methoxamine does not interact with the alB-subtype.Keywords: Iris dilator (rabbit), a,-Adrenoceptor, a113-Subtype, Clonidine, Methoxamine There are two distinct subtypes of a,-adrenoceptors, which are distinguished by their affinities for prazosin and yohimbine in the blood vessels; these were termed alH and alL by Flavahan and Vanhoutte (1) because of their high and low affinity, respectively. These observa tions are in agreement with the results of Takayanagi et al. (2) who demonstrated two subtypes of ai-adreno ceptors in arteries based on their affinities for prazosin and its derivatives. Radioligand binding studies with[3H]prazosin indicated the existence of two separate populations of ai-adrenoceptors that were designated a1A and aiB, respectively (3). A similar subclassification was proposed by Han et al. (4). The alA-subtype has a high affinity for 5-methylurapidil and WB4101 (2-(2,6 dimethoxyphenoxyethyl)-amino methyl-l,4-benzodioxane), while the aiB-subtype has a low affinity for these drugs and is selectively susceptible to chloroethylclonidine. Muramatsu et al. (5) recently proposed that al-adreno ceptors in blood vessels can be divided into three sub types designated as alH, alL and aIN by their antagonist affinity and susceptibility to chloroethylclonidine.Based on the affinity for WB4101 and the susceptibil ity to chloroethylclonidine, Takayanagi et al. (6) re ported that there are both a1A and aiB-subtypes of adrenoceptors in the rabbit common iliac artery and thoracic aorta, although in the thoracic aorta, the amount of alA-adrenoceptors is less than that of alB adrenoceptors (7), and that the full agonists contract them through both subtypes, while the partial agonist induced contraction is mediated through only the alA subtype.Pupil size is autonomically controlled by the sphincter muscles at the pupillary edge of the iris and dilator muscles which run radially on the iris. The dilator mus cles contract through ai-adrenoceptors, and the sphinc ter muscles relax, resulting in mydriasis. Little is known, however, about the subtype of ...