MOLECULAR-IDENTIFICATION AND COEXPRESSION OF GALANIN AND GALR-1 GALANIN RECEPTOR IN THE HUMAN OCULAR CILIARY EPITHELIUM - DIFFERENTIAL MODULATION OF THEIR EXPRESSION BY THE ACTIVATION OF ALPHA(2)-ADRENERGIC AND BETA(2)-ADRENERGIC RECEPTORS IN CULTURED CILIARY EPITHELIAL-CELLS

Here we report the coexpression of the neuropeptide galanin and GalR-1 galanin receptors in the human ciliary epithelium, a bilayer of neuro epithelial cells [nonpigmented (NPE) and pigmented (PE)] with neuroend ocrine functions, and in a cell line (ODM-2) derived from the NPE cell s. Stimulation of ODM-2 cells with phorbol ester [phorbol 12-myristate 13-acetate (PMA)] or forskolin resulted in an up-regulation (two- to threefold) of galanin mRNA expression, Procaterol, a selective beta(2) -adrenergic agonist, and the catecholamine isoproterenol exerted a lon g-term down-regulation on galanin mRNA expression when added alone or in combination with PMA or forskolin. These actions exerted by procate rol or isoproterenol were abolished in the presence of ICI 118,551, a selective beta(2)-adrenergic antagonist. A radioimmunoassay for galani n peptide indicated that galanin or a galaninlike product is present i n the human aqueous humor fluid and is accumulated with time in the cu lture medium of ODM-2 cells. It is interesting that norepinephrine, wh ich exhibited no effect on galanin mRNA expression, induced a down-reg ulation in the level of galanin or galanin-like product accumulated in the medium of cultured ODM-2 cells to levels even lower than those in duced by beta(2)-adrenergic agonists. This effect is best explained by the concomitant up-regulation (four- to fivefold) of GalR-1 galanin r eceptor transcripts induced through the activation of alpha(2)-adrener gic receptors, These findings support the view that pathways elicited by the activation of a,and beta(2)-adrenergic receptors influence the expression of galanin and GalR-1 galanin receptors in ciliary epitheli al cells.