Muscarinic receptor subtypes in human iris-ciliary body measured by immunoprecipitation.
OBJECTIVE
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.
Gil
D W
DW
Department of Biological Sciences, Allergan, Inc., Irvine CA 92612, USA.
Krauss
H A
HA
Bogardus
A M
AM
WoldeMussie
E
E
D000328:Adult; D000368:Aged; D000818:Animals; D016466:CHO Cells; D002648:Child; D002924:Ciliary Body / Q000737:chemistry*; D006224:Cricetinae; D017931:DNA Primers / Q000737:chemistry; D006801:Humans; D007498:Iris / Q000737:chemistry*; D008875:Middle Aged; D009130:Muscle, Smooth / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000145:classification / Q000235:genetics; D014158:Transcription, Genetic
D017931:DNA Primers; D012333:RNA, Messenger; D011976:Receptors, Muscarinic