Cultured human trabecular meshwork cells express functional α2A adrenergic receptors

W. Daniel Stamer, Yi Huang, Richard E.B. Seftor, Samuel S.P. Svensson, Robert W. Snyder, John W. Regan

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Purpose. For the treatment of glaucoma, alpha-2 adrenergic receptor (α2-AR) agonists are thought to lower intraocular pressure primarily by decreasing aqueous humor production. Effects on the outflow pathways, however, also may occur. To begin to examine this possibility, the authors characterized the α2-AR subtypes present in cultures of human trabecular meshwork (HTM) cells using both immunofluorescence microscopy and functional measures of α2-AR activation. Methods. For immunofluorescence microscopy, subtype-specific polyclonal antibodies that recognize each of the human α2- AR subtypes (α2A, α2B, α2C) were used. Functional studies involved the inhibition of forskolin-stimulated cyclic adenosine monophosphate (cAMP) production, the stimulation of mitogen-activated protein (MAP) kinase activity, and the stimulation of mitotic activity as reflected by the expression of proliferating cell nuclear antigen (PCNA). Results. From the immunofluorescence microscopy, there was evidence for the presence of the α2A subtype, but not α2B or α2C subtype, on HTM cells. The administration of the α2-agonist, dexmedetomidine, to HTM cells resulted in a 90% inhibition of forskolin-stimulated cAMP formation, a twofold stimulation of MAP kinase activity, and a threefold increase in the expression of PCNA. Additionally, preincubation of cells with either of the α2-AR-selective antagonists, rauwolscine or atipamezole, reversed the functional effects of dexmedetomidine. Conclusions. Functional α2A-ARs are present on HTM cells where they may affect the outflow pathway during the treatment of glaucoma with α2-AR agonists.

Original languageEnglish (US)
Pages (from-to)2426-2433
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number12
StatePublished - Nov 1996

Keywords

  • adenylyl cyclase
  • cyclic adenosine monosphosphate
  • glaucoma, mitogen- activated protein kinase
  • proliferating cell nuclear antigen

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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