Atypical alpha-adrenoceptor mediates phenylephrine-induced mydriasis in anesthetized cats.
Pupillary dilation and nictitating membrane (NM) contraction were elicited by pharmacological activation of alpha-adrenoceptors in vivo in anesthetized cats. A constant intravenous infusion of the alpha 1-adrenoceptor selective agonist phenylephrine (150 micrograms/min) was administered to produce a near maximal activation of both organs. Steady-state responses were attained about 15 minutes after starting the phenylephrine infusion. Administration of the alpha 1-adrenoceptor selective antagonist prazosin produced a dose-dependent blockade of NM contractions without altering phenylephrine-induced mydriasis when given as pretreatment (1.0 mg/kg i.v.) or post-treatment (0.01-1.0 mg/kg i.v.). In contrast, post-treatment with the alpha 1-adrenoceptor selective antagonist WB-4101 (0.1-1.0 mg/kg i.v.) or pretreatment with phenoxybenzamine (3.0 mg/kg i.v.) blocked both the NM and pupillary responses. These results suggest that the in vivo pupillary response to phenylephrine is mediated by an atypical alpha-adrenoceptor that cannot be readily classified as an alpha 1- or alpha 2-adrenoceptor. In contrast, the alpha-adrenoceptors of the NM appear to be of the classical alpha 1 subtype.
Hey
J A
JA
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City.
Gherezghiher
T
T
Koss
M C
MC
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D002415:Cats; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D009184:Mydriatics / Q000494:pharmacology*; D009541:Nictitating Membrane / Q000187:drug effects*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D009184:Mydriatics; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D011224:Prazosin