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A Berra, MJ Saravia, S Ganzinelli, L Sterin-Borda, E Borda; Activation Of Nitric Oxide Signaling Through M3 And M1 Muscarinic Receptor In Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1442.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Acetylcholine is recognized as a retinal transmitter substance implicated at some points in the visual system. The presence of nicotinic and muscarinic acethycholine receptors (mAChRs) in retina has been described. The aim of the present work was to identify in rat retina mAChR subtypes and determine whether pathways exists in rat retina for mAChRs and nitric oxide (NO), cyclic GMP (cGMP) accumulation. Method: The mRNA expression of both neural nitric oxide synthase (nNOS) and M1 and M3 mAChR subtypes were determinated by RT-PCR. Nitric oxide synthase (NOS) activity was determinated measuring L-[U-14C] citruline using L-[U-14C] arginine as substrate; cyclic GMP (cGMP) by RIA and pharmacological evidence for M1 and M3 mAChR subtypes was assessed using a mAChR agonist (carbachol) and antagonist (pirenzepine, 4-DAMP, AF-DX113). Results: The mRNA expression of both nNOS and M1 and M3 mAChR were demonstrated. Exposure of the rat retina to carbachol (10-11 M to 10-7 M) increased NOS activity and cGMP accumulation in a concentration-dependent manner. Pirenzepine (M1) and 4-DAMP (M3) but not AF-DX113 (M2), blocked these effects. The increase in NOS activity and cGMP content induced by carbachol was blumted by inhibitors of NOS activity (L-NMMA), calcium/calmodulin (TFP) and phospholipase C (U73122) while a protein kinase C (PKC) inhibitor (staurosporine) was without effect Conclusion: These data demostrate that NOS-cGMP pathway exists in retina and that they were linked to the activation of the M1 and M3 mAChR subtypes; contributing in the regulation and/or modulation of photoreceptor cells and various functions in the retina.
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