MUSCARINIC RECEPTOR SUBTYPES IN HUMAN IRIS-CILIARY BODY MEASURED BY IMMUNOPRECIPITATION

Purpose. To determine the relative levels of the five muscarinic recep tor subtypes in the anterior segment of the human eye. Methods. Antise ra selective for each of the five muscarinic receptor proteins were in cubated with [H-3]-QNB bound receptors solubilized from human iris sph incter, ciliary muscle, and ciliary processes, Precipitation of tile r adiolabelled receptor-antibody complexes and scintillation counting en abled quantitation of the subtypes in the various tissues. Reverse tra nscription-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 an d ciliary body are the m3 subtype. Lower levels (5% to 10%) of the m2 and m4 receptors are present in these tissues. The mi receptor (7%) wa s detected in the ciliary processes and iris sphincter and the m5 rece ptor (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 e ye. The extensive heterogeneity of muscarinic receptors makes it diffi cult to predict whether subtype-selective drugs will have an improved efficacy and side-effect profile.