Muscarinic Toxin 3
 

Muscarinic (M) receptors belong to the G-protein coupled receptor family and consist of 5 subtypes, M1-M5, that are activated by acetylcholine (ACh).  The M4 receptor is present primarily on neurons in the central nervous system of mammals; therefore, it is not surprising that recent studies implicate a role for the receptor in memory, learning, psychosis, motor control, and metabolism.  Several studies have found that M4 receptors were significantly reduced in dentate gyrus in Alzheimer’s patients (1) and receptor binding was associated with impaired consciousness and visual hallucinations in Alzheimer’s patients (2). Behavior studies indicate M4 plays a role in regulation of movement and prepulse inhibition of startle reflex, a measure of attention (3). Others have shown that injection of muscarinic toxin 3 (MT3), a M4 receptor antagonist, in rat hippocampus caused amnesia in those animals (4). 

Evidence suggests that M4 receptors also participate in the inhibitory control of dopamine 1 (D1) receptors.  Both receptors can be found in striatonigral neurons (5).  M4 deficient mice have elevated basal locomotive activity and increased locomotive response following activation of D1 receptors (6,7).  Loss of dopamine regulation has been associated with diseases such as Parkinson’s and Schizophrenia. In addition, mounting evidence suggests muscarinic receptors may have a metabolic role in insulin control.  Pretreatment of clonal beta cells with M4 antagonist, MT3, increased ACh-induced insulin secretion by as much as 168% (8)

MT3 is a three finger toxin that consists of 65 amino acids and 4 disulfide bonds.  It was first isolated from Green Mamba venom and was shown to be highly selective for M4 receptor in assays done in CHO cells cloned with human M1-M4 and neuroblastoma cells expressing M4 (9,10,11).  Peptides International currently offers this new, potent selective M4 receptor antagonist for research applications.  MT3 (PMT-4410-s) should provide a valuable tool for investigating the role of this receptor in functional responses and related diseases such as Parkinson’s and Alzheimer’s.
 

Manufactured by the Peptide Institute and Available from Peptides International

Muscarinic Toxins
1) K.N Bradley, Pharmacol. Ther., 85, 87 (2000). (Review)
2) L.T. Potter, Life Sci., 68, 2541 (2001). (Review)

CODE

PRODUCT

QTY

USD

PMT-4410-s
NEW!

 Muscarinic Toxin 3
(Green Mamba, Dendroaspis angusticeps)
[MT3, MTX3, m4-toxin]
Synthetic Product
 Leu-Thr-Cys-Val-Thr-Lys-Asn-Thr-Ile-Phe-Gly-Ile-Thr-Thr-Glu-Asn-Cys-Pro-Ala-Gly-Gln-Asn-Leu-Cys-Phe-Lys-Arg-Trp-His-Tyr- Val-Ile-Pro-Arg-Tyr-Thr-Glu-Ile-Thr-Arg-Gly-Cys-Ala-Ala-Thr-Cys-Pro-Ile-Pro-Glu-Asn-Tyr-Asp-Ser-Ile-His-Cys-Cys-Lys-Thr-Asp-Lys-Cys-Asn-Glu
(Disulfide bonds between Cys3- Cys24, Cys17- Cys42, Cys46- Cys57, and Cys58- Cys63)
(M.W. 7379.40 ) C319H489N89O97S8
Specifc Ligand for Muscarinic Acetylcholine Receptor-4 (M4)
 

1) M. Jolkkonen, P.L.M. van Giersbergen, U. Hellman, C. Wernstedt, and E. Karlsson, FEBS Lett., 352, 91 (1994). (Original; MT3)
2) J.-S. Liang, J. Carsi-Gabrenas, J.L. Krajewski, J.M. McCafferty, S.L. Purkerson, M.P. Santiago, W.L. Strauss, H.H. Valentine, and L.T. Potter, Toxicon, 34, 1257 (1996). (Original; m4-toxin)
3) A. Adem and E. Karlsson, Life Sci., 60, 1069 (1997). (Pharmacol.; Muscarinic Receptor Subtype Specificity)
4) S. Katayama, M. Ishimaru, H. Nishio, Y. Nishiuchi, and T. Kimura, Peptide Science 2004, 161 (2005). (S-S Bond)

0.1 mg vial

315

1. E. Mulugeta, E. Karlsson, A. Islam, R. Kalaria, H. Mangat, B. Winblad, and A. Adem. Brain Res. 960, 259 (2003).
2. T. Teaktong, M.A. Piggott, I.G. Mckeith, R.H. Perry, C.G. Ballard, and E.K. Perry. Behav. Brain Res., 161, 299 (2005).
3. C.C. Felder, A.C. Porter, T.L. Skillman, L. Zhang, F.P. Bymaster, N.M. Nathanson, S.E. Hamilton, J. Gomeza, J. Wess, and D.L. McKinzie. Life Sci., 68, 2605 (2001).
4. D. Jerusalinsky, E. Kornisiuk, P. Alfaro, J. Quillfeldt, M. Alonso, E.R. Verde, C. Cervenansky, and A Harvey, Neuroreport, 9, 1407 (1998).
5. E. Ince, B.J. Ciliax, and A.I. Levey. Synapse, 27, 357 (1997).
6. J. Gomeza, L. Zhang, E. Kostenis, C.C. Felder, F.P. Bymaster, J. Broadkin, H. Shannon, B. Xia, A. Duttaroy, C.X. Deng, and J. Wess. Life Sci., 68, 2457 (2001).
7. J. Gomeza, L. Zhang, E. Kostenis, C. Felder, F. Bymaster, J. Brodkin, H. Shannon, B. Xia, C. Deng, and J. Wess. Neurobiology, 96, 10483 (1999).
8. J.C. Miguel, Y.H. Abdel-Wahab, P.C. Mathias, and P.R. Flatt. Biochem Biophys. Acta., 1569, 45 (2002).
9. E. Karlsson, M. Jolkkonen, N. Satyapan, A. Adem, E. Kumlin, U. Hellman, and C. Wernstedt, Ann. NY Acad. Sci., 710, 153 (1994).
10. M. Jolkkonen, P.L. van Giersbergen, U. Hellman, C. Wernstedt, and E. Karlsson. FEBS Lett., 352, 91 (1994).
11. M.C. Olianas, A. Ingianni, C. Maullu, A. Adem, E. Karlsson, and P. Onali., J. Pharmacol. Exp. Ther. 288, 164 (1999).

Please contact our technical sales specialists to discuss your project needs and for custom inquiries.

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Peptides International, Inc.
PO Box 24658
Louisville, Kentucky 40224 USA
Phone: 502-266-8787 or 800-777-4779
Fax: 502-267-1FAX (1329)
Email:  peptides@pepnet.com

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