Neuropeptide Y suppresses the neurogenic inflammatory response in the rabbit eye; mode of action.
Ocular injury in the rabbit causes miosis and breakdown of the blood aqueous barrier (aqueous flare response, AFR), reflecting a sensory nerve-mediated inflammatory response, elicited by the release of tachykinins and calcitonin gene-related peptide (CGRP) from C-fibers. Neuropeptide Y (NPY) occurs in sympathetic fibers in the eye. The study was designed to examine whether NPY and related peptides interfere with the inflammatory response to ocular injury in the rabbit in vivo. The isolated rabbit iris was studied with respect to NPY binding sites and second messenger coupling. The AFR and the miotic response to a standardized injury (infrared irradiation (IR) of the iris) were suppressed dose-dependently by NPY (0.01-1.0 nmol) injected intravitreally 30 min prior the trauma. The treated eye was compared with the contralateral eye, which received 0.9% saline and IR. The Y1 receptor agonist [Pro34]NPY, the Y2 receptor agonist NPY 13-36 and the structurally related peptide YY (1 nmol each) suppressed the AFR in response to IR. Injection of either NPY or the Y1 and Y2 receptor agonists (0.3 nmol each) suppressed the AFR evoked by exogenously applied CGRP (0.15 nmol). Saturation studies with 125I-NPY revealed both high and 'moderate' affinity binding sites in the iris. The Bmax values were 26 and 321 fmol/mg protein, respectively. NPY suppressed the forskolin-stimulated adenylate cyclase activity (IC50 value 19 nM). NPY did not affect basal or noradrenaline-induced accumulation of inositol phosphates in the iris. In conclusion, the rabbit iris seems to be rich in NPY receptors linked to inhibition of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Grundemar
L
L
Department of Clinical Pharmacology, University of Lund, Sweden.
Wahlestedt
C
C
Wang
Z Y
ZY
D000262:Adenylyl Cyclases / Q000378:metabolism; D000320:Adrenergic Fibers / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007498:Iris / Q000187:drug effects* / Q000378:metabolism; D007500:Iritis / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*
D007295:Inositol Phosphates; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C062924:neuropeptide Y (13-36); D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide