Alpha-2 adrenoceptor mediated changes in aqueous dynamics: effect of pertussis toxin

Exp Eye Res. 1994 Jun;58(6):729-36. doi: 10.1006/exer.1994.1070.

Abstract

Because alpha-2 (alpha 2) adrenoceptor-mediated inhibition of signal transduction mechanisms is regulated, in part, by inhibitory G (Gi) protein, we studied the effects of pertussis toxin (PTX) pretreatment on alpha 2 adrenergic agonist, UK 14,304-18 (UK; brimonidine)-induced: (1) changes in intraocular pressure (IOP) and aqueous flow rate of rabbits; (2) modulation of 3H-norepinephrine (NE) overflow of rabbit iris-ciliary bodies (ICBs) and (3) accumulation of cyclic AMP in rabbit ICBs and cultured non-pigmented ciliary epithelial (NPE) cells. Results showed that UK (50 micrograms) lowered the IOP of normal rabbits by 8 +/- 1 mmHg (n = 8) at 3 hr when treated topically and that the reduction of IOP was accompanied by a decrease in aqueous humor inflow (35%, n = 5). Therefore, it was postulated that these UK-induced effects involve activation of a Gi protein linked to alpha 2 adrenoceptors. In PTX-pretreated (2.5 micrograms kg-1, i.a.) rabbits, hypotensive responses to UK were reduced by 50% and 70% (n = 8) at days 4 and 7 post PTX treatment, respectively. The suppression of aqueous humor inflow induced by UK was also prevented by the PTX treatment. In isolated, perfused rabbit ICBs, UK (1 microM) caused 50% inhibition of 3H-NE overflow from electrical field stimulation. Pretreatment with PTX (150 ng ml-1, 4 hr) partially prevented UK-induced inhibition of NE overflow. In in vitro assays of postjunctional alpha 2 adrenoceptor activity, UK (1 microM) inhibited isoproterenol (ISO, 1 microM)-stimulated cAMP accumulation by 45% and 48% in ICBs and NPE cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / metabolism*
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Antihypertensive Agents / antagonists & inhibitors*
  • Antihypertensive Agents / pharmacology
  • Aqueous Humor / drug effects*
  • Aqueous Humor / physiology
  • Brimonidine Tartrate
  • Cyclic AMP / metabolism
  • Intraocular Pressure / drug effects
  • Kinetics
  • Norepinephrine / metabolism
  • Pertussis Toxin*
  • Quinoxalines / antagonists & inhibitors*
  • Quinoxalines / pharmacology
  • Rabbits
  • Uvea / metabolism
  • Virulence Factors, Bordetella / pharmacology*

Substances

  • Adrenergic alpha-Agonists
  • Antihypertensive Agents
  • Quinoxalines
  • Virulence Factors, Bordetella
  • Brimonidine Tartrate
  • Cyclic AMP
  • Pertussis Toxin
  • Norepinephrine