Functional characterization of α-adrenoceptors mediating pupillary dilation in rats

Abstract

Previously, we reported that the α 1A-adrenoceptor, but not the α 1D-adrenoceptor, mediates pupillary dilation elicited by sympathetic nerve stimulation in rats. This study was undertaken to further characterize the α-adrenoceptor subtypes mediating pupillary dilation in response to both neural and agonist activation. Pupillary dilator response curves were generated by intravenous injection of norepinephrine in pentobarbital-anesthetized rats. Involvement of α 1-adrenoceptors was established as mydriatic responses were inhibited by systemic administration of nonselective α-adrenoceptor antagonists, phentolamine (0.3–3 mg/kg) and phenoxybenzamine (0.03–0.3 mg/kg), as well as by the selective α 1-adrenoceptor antagonist, prazosin (0.3 mg/kg). The α 2-adrenoceptor antagonist, rauwolscine (0.5 mg/kg), was without antagonistic effects. α 1A-Adrenoceptor selective antagonists, 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101; 0.1–1 mg/kg) and 5-methylurapidil (0.1–1 mg/kg), the α 1B-adrenoceptor selective antagonist, 4-amino-2-[4-[1-(benzyloxycarbonyl)-2( S)- [[(1,1-dimethylethyl)amino]carbonyl]-piperazinyl]-6,7-dimethoxyquinazoline (L-765314; 0.3–1 mg/kg), as well as the α 1D-adrenoceptor selective antagonist, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY-7378; 1 mg/kg), were used to delineate the adrenoceptor subtypes involved. Mydriatic responses to norepinephrine were significantly antagonized by intravenous administration of both WB-4101 and 5-methylurapidil, but neither by L-765314 nor by BMY-7378. L-765314 (0.3–3 mg/kg, i.v.) was also ineffective in inhibiting the mydriasis evoked by cervical sympathetic nerve stimulation. These results suggest that α 1B-adrenoceptors do not mediate sympathetic mydriasis in rats, and that the α 1A-adrenoceptor is the exclusive subtype mediating mydriatic responses in this species.