FIve distinct but related muscarinic receptors had been identified. These glycosylated proteins have single chains of 460 to 590 amino acids that
are thought to span the plasma membrane 7 times, creating 4 extracellular domains, 7 helical hydrophobic
transmembrane domains, and 4 intracellular domains. Each protein is the product of a different gene without introns in
the coding sequence, and the amino acid sequences in the receptor subtypes are remarkably homologous among different
animal species.
NCBI Summary:
The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine to these receptors and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and postassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 1 is involved in mediation of vagally-induced bronchoconstriction and in the acid secretion of the gastrointestinal tract. The gene encoding this receptor is localized to 11q13, with MDU1 proximally and COX8 distally located.
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Comment
Soboloff J, et al 1995 reported the influence of the muscarinic agonist carbachol on intracellular Ca2+ in chicken
granulosa cells.
Mayerhofer A, et al 1992 reported that carbachol treatment increases intracellular free calcium concentrations in human
granulosa-lutein cells.
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
Fritz S, et al 2001 reported the expression of muscarinic receptor types in the primate ovary
and evidence for nonneuronal acetylcholine synthesis.
Because luteinized human granulosa cells (GC) in culture express
functional MR, the authors have determined whether the group of the related MR
subtypes, M1R, M3R, and M5R, are present in vivo in human and rhesus monkey
ovaries. To this end, ribonucleic acids (RNAs) of different human and monkey
ovaries as well as RNAs from human GC and monkey oocytes were reverse
transcribed and subjected to PCR amplification, followed by sequencing of the
amplified complementary DNAs. Results obtained showed that M1R, M3R, and M5R
messenger RNAs are present in adult human and monkey ovaries; oocytes express
exclusively the M3R subtype, whereas GC express M1R and M5R.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Fritz S, et al 2002 reported that activation of muscarinic receptors in human luteinized granulosa cells blocks gap junctions and induces the transcription
factor early growth response factor-1.
Cholinergic agents increase intracellular
calcium levels and stimulate granulosa cell (GC) proliferation via muscarinic receptors. Based
on this observation and because endocrine cells of the forming human corpus
luteum (CL), which are the in vivo counterparts of GCs, also proliferate in
vivo, the authors hypothesized that ACh may be a factor involved in the regulation of
the complex cellular events occurring during ovulation and formation of the
CL. Normally, cultured GCs and their in vivo
counterparts are coupled via gap junctions (GJ) consisting of connexin 43.
Treatment with carbachol impaired GJ coupling of GCs within seconds, as shown
in single cell, whole cell, patch-clamp studies. The cholinergic antagonist
atropine and the muscarinic receptor antagonist pirenzepine specifically
blocked this effect. Disruption of GJ communication of GCs is probably due to increased phosphorylation of connexin 43 at serine residues, as shown in
immunoprecipitation experiments with carbachol-challenged GCs.
Ovulation/formation of the CL include reprogramming of luteinizing cells, and
in the rat this involves gonadotropin-induced expression of the transcription
factor early growth response factor-1 (egr-1). In human GCs ,
carbachol as well as hCG can mimic this effect, as shown by cDNA arrays and
semiquantitative RT-PCR. In conclusion,endogenous, locally produced ACh may contribute to the cellular
remodeling of the forming CL via muscarinic receptor/egr-1, thereby affecting
proliferation, GJ communication, and regulation of gene expression in
luteinizing granulosa cells.