title: Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill.
abstract: BACKGROUND
  In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents.
  
  
  RESULTS
  The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl) carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion.
  
  
  CONCLUSIONS
  Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion.
authors.affiliation: Department of Biology, Texas State University-San Marcos, Texas 78666, USA. trinityfinancial@sbcglobal.net
authors.forename: Alfredo
authors.initials: A
authors.lastname: González
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Crittenden
authors.forename: Dana M
authors.initials: DM
authors.lastname: García
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D008027:Light; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010473:Perciformes / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects / Q000648:ultrastructure; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors; D043588:Receptor, Muscarinic M4 / Q000037:antagonists & inhibitors; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012168:Retinal Pigments / Q000032:analysis*; D015290:Second Messenger Systems / Q000187:drug effects; D014331:Tropicamide / Q000494:pharmacology
chemical_list: C496641:4-(N-(4-chlorophenyl)carbamoyloxy)-4-pent-2-ammonium iodide; D000067956:Adenylyl Cyclase Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D000644:Quaternary Ammonium Compounds; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D012168:Retinal Pigments; C015000:arecaidine esters; D005576:Colforsin; D010890:Pirenzepine; D001115:Arecoline; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; D000242:Cyclic AMP; D014331:Tropicamide; C048593:otenzepad