PURPOSE: To determine the relative levels of the five muscarinic receptor subtypes in the anterior segment of the human eye. METHODS: Antisera selective for each of the five muscarinic receptor proteins were incubated with [3H]-QNB bound receptors solubilized from human iris sphincter, ciliary muscle, and ciliary processes. Precipitation of the radiolabeled receptor-antibody complexes and scintillation counting enabled quantitation of the subtypes in the various tissues. Reverse transcription-polymerase chain reaction was performed on the tissues and cultured smooth muscle cells derived from them. RESULTS: Approximately 60% to 75% of the muscarinic receptors in the human iris sphincter and ciliary body are the m3 subtype. Lower levels (5% to 10%) of the m2 and m4 receptors are present in these tissues. The m1 receptor (7%) was detected in the ciliary processes and iris sphincter and the m5 receptor (5%), which is usually found only in the central nervous system, was present in the iris sphincter. CONCLUSIONS: The m3 subtype is the predominant muscarinic receptor in the anterior segment of the human eye. The extensive heterogeneity of muscarinic receptors makes it difficult to predict whether subtype-selective drugs will have an improved efficacy and side-effect profile.
PURPOSE: To determine the relative levels of the five muscarinic receptor subtypes in the anterior segment of the human eye. METHODS: Antisera selective for each of the five muscarinic receptor proteins were incubated with [3H]-QNB bound receptors solubilized from humaniris sphincter, ciliary muscle, and ciliary processes. Precipitation of the radiolabeled receptor-antibody complexes and scintillation counting enabled quantitation of the subtypes in the various tissues. Reverse transcription-polymerase chain reaction was performed on the tissues and cultured smooth muscle cells derived from them. RESULTS: Approximately 60% to 75% of the muscarinic receptors in the humaniris sphincter and ciliary body are the m3 subtype. Lower levels (5% to 10%) of the m2 and m4 receptors are present in these tissues. The m1 receptor (7%) was detected in the ciliary processes and iris sphincter and the m5 receptor (5%), which is usually found only in the central nervous system, was present in the iris sphincter. CONCLUSIONS: The m3 subtype is the predominant muscarinic receptor in the anterior segment of the human eye. The extensive heterogeneity of muscarinic receptors makes it difficult to predict whether subtype-selective drugs will have an improved efficacy and side-effect profile.
Authors: M Yamada; K G Lamping; A Duttaroy; W Zhang; Y Cui; F P Bymaster; D L McKinzie; C C Felder; C X Deng; F M Faraci; J Wess Journal: Proc Natl Acad Sci U S A Date: 2001-11-13 Impact factor: 11.205
Authors: Paul Abrams; Karl-Erik Andersson; Jerry J Buccafusco; Christopher Chapple; William Chet de Groat; Alison D Fryer; Gary Kay; Alan Laties; Neil M Nathanson; Pankaj Jay Pasricha; Alan J Wein Journal: Br J Pharmacol Date: 2006-06-05 Impact factor: 8.739
Authors: Jason Y H Chang; W Daniel Stamer; Jacques Bertrand; A Thomas Read; Catherine M Marando; C Ross Ethier; Darryl R Overby Journal: Am J Physiol Cell Physiol Date: 2015-06-03 Impact factor: 4.249