title: Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats.
abstract: Previously, we reported that the alpha(1A)-adrenoceptor, but not the alpha(1D)-adrenoceptor, mediates pupillary dilation elicited by sympathetic nerve stimulation in rats. This study was undertaken to further characterize the alpha-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 alpha(1)-adrenoceptors was established as mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenoceptor antagonists, phentolamine (0.3-3 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as by the selective alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg). The alpha(2)-adrenoceptor antagonist, rauwolscine (0.5 mg/kg), was without antagonistic effects. alpha(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 alpha(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 alpha(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 alpha(1B)-adrenoceptors do not mediate sympathetic mydriasis in rats, and that the alpha(1A)-adrenoceptor is the exclusive subtype mediating mydriatic responses in this species.
authors.affiliation: Department of Cell Biology, University of Oklahoma College of Medicine, Oklahoma City, OK 73190, USA. yongxin-yu@ouhsc.edu
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Yu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Koss
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D004146:Dioxanes / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007275:Injections, Intravenous; D008297:Male; D015878:Mydriasis / Q000139:chemically induced* / Q000517:prevention & control; D009638:Norepinephrine / Q000008:administration & dosage / Q000493:pharmacokinetics; D010643:Phenoxybenzamine / Q000008:administration & dosage / Q000493:pharmacokinetics; D010646:Phentolamine / Q000008:administration & dosage / Q000493:pharmacokinetics; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D011224:Prazosin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011680:Pupil / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology*; D015016:Yohimbine / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; C111640:L 765314; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D010643:Phenoxybenzamine; C057446:5-methylurapidil; D015016:Yohimbine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C053428:BMY 7378; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine