{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:29:03Z","timestamp":1793410143665,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Pilocarpine, a muscarinic receptor agonist, is clinically used to reduce intraocular pressure via ciliary muscle contraction. However, the intracellular signaling pathways mediating pilocarpine\u2010induced nitric oxide (\n NO<\/jats:styled-content>\n ) and prostaglandin E\n 2<\/jats:sub>\n (\n \n PGE\n 2<\/jats:sub>\n <\/jats:styled-content>\n ) synthesis in the ciliary muscle are not fully understood. This study aimed to characterize the muscarinic receptor subtypes and intracellular mechanisms involved in pilocarpine\u2010induced\n NO<\/jats:styled-content>\n and\n \n PGE\n 2<\/jats:sub>\n <\/jats:styled-content>\n production in porcine ciliary muscle and to explore the potential implications of these pathways in age\u2010related ocular changes, including presbyopia. Ciliary muscle strips from adult porcine eyes were incubated in Krebs\u2010Ringer buffer with pharmacological agents. Nitrate levels were measured using a Griess reaction\u2010based colorimetric assay, and\n \n PGE\n 2<\/jats:sub>\n <\/jats:styled-content>\n concentrations were quantified via\n ELISA<\/jats:styled-content>\n . Selective receptor antagonists and enzyme inhibitors were used to investigate receptor involvement and signaling cascades. Statistical significance was determined using unpaired\n t<\/jats:italic>\n \u2010tests (\n p<\/jats:italic>\n \u2009<\u20090.05). Pilocarpine elicited a concentration\u2010dependent increase in nitrate and\n \n PGE\n 2<\/jats:sub>\n <\/jats:styled-content>\n production, peaking at 1\u2009\u00d7\u200910\n \u22127<\/jats:sup>\n \u2009M. This effect was inhibited by atropine, pirenzepine (\n \n M\n 1<\/jats:sub>\n <\/jats:styled-content>\n antagonist), and\n J104129<\/jats:styled-content>\n (\n \n M\n 3<\/jats:sub>\n <\/jats:styled-content>\n antagonist), but not by the\n \n M\n 2<\/jats:sub>\n <\/jats:styled-content>\n antagonist\n AFDX<\/jats:styled-content>\n 116. Inhibitors of nitric oxide synthase (L\u2010\n NMMA<\/jats:styled-content>\n , L\u2010\n NIO<\/jats:styled-content>\n ), phospholipase C (U\u201073122), cyclooxygenase (diclofenac), and calcium signaling (verapamil,\n TFP<\/jats:styled-content>\n ) all reduced mediator production, while calcium ionophore\n A23187<\/jats:styled-content>\n enhanced it. Pilocarpine activates\n \n M\n 1<\/jats:sub>\n <\/jats:styled-content>\n and\n \n M\n 3<\/jats:sub>\n <\/jats:styled-content>\n muscarinic receptors in the porcine ciliary muscle, stimulating\n NO<\/jats:styled-content>\n and\n PGE<\/jats:styled-content>\n 2<\/jats:sub>\n production via calcium\u2010dependent\n PLC<\/jats:styled-content>\n \u2013\n NOS<\/jats:styled-content>\n \u2013\n COX<\/jats:styled-content>\n signaling. These pathways may influence ciliary muscle function and lens physiology, offering potential therapeutic targets for glaucoma and presbyopia.\n <\/jats:p>","DOI":"10.1096\/fba.2025-00161","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T15:02:03Z","timestamp":1761836523000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms of Pilocarpine\u2010Induced Nitric Oxide and Prostaglandin Production in Porcine Ciliary Muscle"],"prefix":"10.1096","volume":"7","author":[{"given":"Giovanna","family":"Benozzi","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Avanzada Para la Presbicia Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Quinteros Villarruel","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, Facultad de Odontolog\u00eda, Universidad de Buenos Aires Buenos Aires 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