Alpha-Adrenergic Agonists Stimulate Fluid Secretion in Lacrimal Gland Ducts

Invest Ophthalmol Vis Sci. 2020 Dec 1;61(14):3. doi: 10.1167/iovs.61.14.3.

Abstract

Purpose: The role of adrenergic innervation in the regulation of lacrimal gland (LG) ductal fluid secretion is unknown. The Aim of the present study was to investigate the effect of adrenergic stimulation on fluid secretion in isolated LG duct segments and to study the underlying intracellular mechanisms.

Methods: Fluid secretion of isolated mouse LG ducts was measured using video-microscopy. Effect of various adrenergic agonists (norepinephrine, phenylephrine, and isoproterenol) on fluid secretion as well as inhibitory effects of specific antagonists on adrenergic agonist-stimulated secretory response were analyzed. Changes in intracellular Ca2+ level [Ca2+i] were investigated with microfluorometry.

Results: Both norepinephrine and phenylephrine initiated a rapid and robust fluid secretory response, whereas isoproterenol did not cause any secretion. Phenylephrine-induced secretion was completely blocked by α1D-adrenergic receptor blocker BMY-7378. The endothelial nitric oxide synthase (eNOS) inhibitor L-NAME or guanylyl cyclase inhibitor ODQ reduced but not completely abolished the phenylephrine-induced fluid secretion, whereas co-administration of Ca2+-chelator BAPTA-AM resulted in a complete blockade. Phenylephrine stimulation induced a small, but statistically significant elevation in [\(Ca_i^{2 + }\)].

Conclusions: Our results prove the direct role of α1-adrenergic stimulation on LG ductal fluid secretion. Lack of isoproterenol-induced fluid secretory response suggests the absence of β-receptor mediated pathway in mouse LG ducts. Complete blockade of phenylephrine-induced fluid secretion by BMY-7378 and predominant inhibition of the secretory response either by L-NAME or ODQ suggest that α-adrenergic agonists use the NO/cGMP pathway through α1D receptor. Ca2+ signaling independent from NO/cGMP pathway may also play an at least partial role in α-adrenergic induced ductal fluid secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Calcium / metabolism
  • Cytophotometry
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Lacrimal Apparatus / drug effects*
  • Mice
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nasolacrimal Duct / drug effects*
  • Nasolacrimal Duct / metabolism
  • Norepinephrine / pharmacology
  • Phenylephrine / pharmacology
  • Piperazines / pharmacology
  • Tears / drug effects

Substances

  • Adrenergic alpha-Agonists
  • Piperazines
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Phenylephrine
  • Egtazic Acid
  • BMY 7378
  • Calcium
  • NG-Nitroarginine Methyl Ester
  • Norepinephrine