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CHRM1  -  cholinergic receptor, muscarinic 1

Macaca mulatta

 
 
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Disease relevance of M1

  • The M1 antagonist pirenzepine was at least 30-fold less potent, with IC50 values of 2.2 microM for outflow facility, 1.4 microM for accommodation and 0.1 microM for miosis [1].
  • Centrally-mediated hypothermia was induced by RS86 (0.05 mg/kg p.o.) and L-689,660 (0.01 mg/kg p.o.) but only by a high dose of AF 102B (7 mg/kg p.o.). The putative therapeutic advantages of partial M1/M3 agonists over RS86 are discussed [2].
  • The effect of leukocyte depletion on pulmonary M2 muscarinic receptor function in parainfluenza virus-infected guinea-pigs [3].
 

High impact information on M1

  • Selective expression of m2 muscarinic receptor in the parvocellular channel of the primate visual cortex [4].
  • Association of m1 and m2 muscarinic receptor proteins with asymmetric synapses in the primate cerebral cortex: morphological evidence for cholinergic modulation of excitatory neurotransmission [5].
  • Using immunohistochemistry with specific antibodies to recombinant m1 and m2 muscarinic receptor proteins, we have demonstrated that both m1 and m2 receptors are prominently associated with noncholinergic asymmetric synapses as well as with the symmetric synapses that characterize the cholinergic pathways in the neocortex [5].
  • The concentration of both muscarinic (M1 and M2) and nicotinic receptor binding sites declined with increasing age, and decrements were uniform across all cortical layers [6].
  • Expression of muscarinic receptor types in the primate ovary and evidence for nonneuronal acetylcholine synthesis [7].
 

Chemical compound and disease context of M1

 

Biological context of M1

  • A selective M1 receptor antagonist pirenzepine did not affect ACh-induced vasoconstriction significantly and inhibited the vasodilation partially only at the highest dose (100 nmol) [9].
  • In dogs, the two muscarinic receptor agonists produced only vasodilatation [10].
 

Anatomical context of M1

  • Although high-affinity 3H-PZ, low-affinity 3H-NMS binding (M1 sites) and high-affinity 3H-OXO-M, high-affinity 3H-NMS binding (M2 sites) occurred across all layers of the temporal neocortex, the laminar distribution of M1 and M2 receptor binding sites was different [6].
  • The overall density of M1 and M2 receptor subtypes was similar throughout the cerebral cortex [11].
  • Almost all limbic and paralimbic regions including the amygdala, hippocampus, orbitofrontal, temporopolar, parahippocampal, cingulate, and parolfactory areas displayed peak densities of the M1 receptor subtype [12].
  • The M1 receptor subtype was prevalent in the dentate gyrus, the CA4-CA3 region, and the CA1 ammonic sector [12].
  • In cortical regions of the parietal and occipital lobes and in the primary motor cortex of the frontal lobe, both M1 and M2 receptor subtypes were concentrated in the supragranular layers [11].
 

Associations of M1 with chemical compounds

  • In the hippocampal formation, M1, M2, and nicotine receptors were distributed differentially, with each subdivision having a specific complement of cholinergic receptor subtype [12].
  • Quantitative autoradiographic localization of the M1 and M2 subtypes of muscarinic acetylcholine receptors in the monkey brain [13].
  • We compare the central and peripheral cholinergic effects of RS86 with the M1/M3 partial agonists AF 102B and L-689,660 ((-)-3-[2-6 chloropyrazin)yl]-1-azabicyclo[2.2.2]octane) in primates [2].
  • A selective M1 receptor agonist 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium++ + chloride (McN-A-343) did not affect the perfusion pressure of the precontracted coronary arteries significantly [9].
  • Milameline (CI-979/RU35926): a muscarinic receptor agonist with cognition-activating properties: biochemical and in vivo characterization [14].
 

Other interactions of M1

  • However, equilibrium binding assays alone have not permitted a clear demonstration of the localization of putative M1, M2, and M3 receptor subtypes in the brain because of the overlapping affinities of virtually all muscarinic antagonists [15].
 

Analytical, diagnostic and therapeutic context of M1

References

  1. Inhibition of outflow facility and accommodative and miotic responses to pilocarpine in rhesus monkeys by muscarinic receptor subtype antagonists. Gabelt, B.T., Kaufman, P.L. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  2. Comparison of the effects of selective and nonselective muscarinic agonists on cognition and thermoregulation in primates. Rupniak, N.M., Tye, S.J., Iversen, S.D. J. Neurol. Sci. (1992) [Pubmed]
  3. The effect of leukocyte depletion on pulmonary M2 muscarinic receptor function in parainfluenza virus-infected guinea-pigs. Fryer, A.D., Yarkony, K.A., Jacoby, D.B. Br. J. Pharmacol. (1994) [Pubmed]
  4. Selective expression of m2 muscarinic receptor in the parvocellular channel of the primate visual cortex. Mrzljak, L., Levey, A.I., Rakic, P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. Association of m1 and m2 muscarinic receptor proteins with asymmetric synapses in the primate cerebral cortex: morphological evidence for cholinergic modulation of excitatory neurotransmission. Mrzljak, L., Levey, A.I., Goldman-Rakic, P.S. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  6. Laminar organization and age-related loss of cholinergic receptors in temporal neocortex of rhesus monkey. Wagster, M.V., Whitehouse, P.J., Walker, L.C., Kellar, K.J., Price, D.L. J. Neurosci. (1990) [Pubmed]
  7. Expression of muscarinic receptor types in the primate ovary and evidence for nonneuronal acetylcholine synthesis. Fritz, S., Wessler, I., Breitling, R., Rossmanith, W., Ojeda, S.R., Dissen, G.A., Amsterdam, A., Mayerhofer, A. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  8. Inhibition of aceclidine-stimulated outflow facility, accommodation and miosis in rhesus monkeys by muscarinic receptor subtype antagonists. Gabelt, B.T., Kaufman, P.L. Exp. Eye Res. (1994) [Pubmed]
  9. Muscarinic receptor subtypes mediating vasodilation and vasoconstriction in isolated, perfused simian coronary arteries. Ren, L.M., Nakane, T., Chiba, S. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
  10. Comparison of the responses of the simian and canine coronary circulations to autonomic drugs. Satoh, K., Yamashita, S., Maruyama, M., Taira, N. J. Cardiovasc. Pharmacol. (1982) [Pubmed]
  11. Regional differences in the distribution of muscarinic cholinergic receptors in the macaque cerebral cortex. Lidow, M.S., Gallager, D.W., Rakic, P., Goldman-Rakic, P.S. J. Comp. Neurol. (1989) [Pubmed]
  12. Distribution of muscarinic receptor subtypes within architectonic subregions of the primate cerebral cortex. Mash, D.C., White, W.F., Mesulam, M.M. J. Comp. Neurol. (1988) [Pubmed]
  13. Quantitative autoradiographic localization of the M1 and M2 subtypes of muscarinic acetylcholine receptors in the monkey brain. Miyoshi, R., Kito, S., Shimoyama, M. Jpn. J. Pharmacol. (1989) [Pubmed]
  14. Milameline (CI-979/RU35926): a muscarinic receptor agonist with cognition-activating properties: biochemical and in vivo characterization. Schwarz, R.D., Callahan, M.J., Coughenour, L.L., Dickerson, M.R., Kinsora, J.J., Lipinski, W.J., Raby, C.A., Spencer, C.J., Tecle, H. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  15. Distinct kinetic binding properties of N-[3H]-methylscopolamine afford differential labeling and localization of M1, M2, and M3 muscarinic receptor subtypes in primate brain. Flynn, D.D., Mash, D.C. Synapse (1993) [Pubmed]
  16. Regional brain distribution and binding of the muscarinic receptor agonist CI-979 studied by positron emission tomography in the monkey. Hartvig, P., Torstenson, R., Bjurling, P., Fasth, K.J., Längström, B., Nordberg, A. Dementia and geriatric cognitive disorders. (1997) [Pubmed]
 
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