AJP - Gastrointestinal and Liver Physiology, Vol 257, Issue 1 151-G156, Copyright © 1989 by American Physiological Society
Inhibition of stimulated lacrimal secretion by [D-Ala2]Met-enkephalinamide
M. M. Cripps and K. Patchen-Moor
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
The synthetic enkephalin analogue, [D-Ala2]Met-enkephalinamide (DALA) was
used to investigate opioid peptide modulation of lacrimal protein
secretion. By use of an in vitro perifusion system, the secretion of
peroxidase by rat lacrimal gland fragments was measured during continuous
stimulation for up to 60 min. DALA had no effect on unstimulated secretion
of peroxidase. However, the addition of DALA to the perifusion medium
resulted in a dose-dependent (10 nM-10 microM) inhibition of
carbachol-stimulated peroxidase release. The maximum effect of DALA was
achieved at a dose of 10 microM, which resulted in a 54% inhibition of
carbachol-induced secretion. The opiate antagonist naloxone (10 nM-10
microM) did not alter basal or carbachol-stimulated peroxidase release. The
effect on 10 microM carbachol-stimulated secretion by the addition of 3
microM DALA, however, was reversed in a dose-dependent manner by naloxone.
The extent of inhibition of vasoactive intestinal peptidergic (VIPergic)
stimulation (50 nM VIP) by DALA was similar to the inhibition of
cholinergic stimulation of peroxidase release by gland fragments. Neither
alpha 1-adrenergic stimulation of secretion nor a synergistic stimulation
by VIP and carbachol was inhibited by the enkephalin analogue. We conclude
that DALA exerts an inhibitory modulation of cholinergic and VIPergic
stimulation of in vitro lacrimal protein secretion and suggest a
physiological role for methionine enkephalin as an inhibitory peptide
involved in the regulation of lacrimal gland function.
