title: Selective alpha 1A-adrenoceptor stimulation induces Mueller's smooth muscle contraction in an isolated canine upper eyelid preparation.
abstract: OBJECTIVE
  It has been demonstrated that in patients with aponeurotic blepharoptosis, alpha(1)-adrenoceptor stimulation causes the contraction of the upper eyelid tarsal smooth muscle (Mueller's muscle) and opening of the eye. However, alpha(1)-adrenoceptor subtypes mediating the contraction of Mueller's muscle are still unclear. This study was designed to identify the alpha(1)-adrenoceptor subtypes in Mueller's muscle.
  
  
  METHODS
  A newly developed canine upper eyelid preparation was retrogradely perfused with a drug-containing Krebs-Henseleit solution through the angular vein in a temperature-controlled organ chamber. The contraction of the preparation was measured with a force-displacement transducer.
  
  
  RESULTS
  Phenylephrine, an alpha(1)-adrenoceptor agonist, increased the upper eyelid contractile force in a dose-dependent manner (K(0.5) = 110 nmol). Interestingly, the contraction in response to phenylephrine was persistent and hardly recovered to a base line level for more than 100 min after washout of the drug. WB4101 (100 nM), an alpha(1A)- and alpha(1D)-adrenoceptor antagonist, but not BMY7378 (100 nM), a selective alpha(1D)-adrenoceptor antagonist, competitively inhibited the phenylephrine-induced contraction. ABT-866, a selective alpha(1A)-adrenoceptor agonist, increased the upper eyelid contractile force as effectively as phenylephrine in a dose-dependent manner (K(0.5) = 190 nmol), and the contraction continued again for more than 100 min.
  
  
  CONCLUSIONS
  These results suggest that selective alpha(1A)-adrenoceptor agonists, such as ABT-866, induce the sustained Mueller's muscle contraction and may be useful in pharmacological treatment of blepharoptosis.
authors.affiliation: Department of Molecular Pharmacology, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Shiharu
authors.initials: S
authors.lastname: Yano
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hirose
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakada
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsuo
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005143:Eyelids / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C466636:ABT 866; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D010656:Phenylephrine