MCD peptide

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The amino acid sequence of MCD peptide [1]
Met - Cys - Ile - Cys - Lys - Asn - Gly - Lys - Pro - Leu - Pro - Gly - Phe - Ile - Gly - Lys - Ile - Cys - Arg - Lys - Ile - Cys - Met - Met - Gln - Gln -Thr - His(NH2)

Mast cell degranulating (MCD) peptide is a cationic 22-amino acid residue peptide, which is a component of the venom of the bumblebee (Megabombus pennsylvanicus). At low concentrations, MCD peptide can stimulate mast cell degranulation. At higher concentrations, it has anti-inflammatory propterties. In addition, it is a potent blocker of voltage-sensitive potassium channels.

Sources

MCD peptide is a component of bumblebee (Megabombus pennsylvanicus) venom.[2] In addition to MCD peptide, melittin and apamin have also been identified in this venom and are also described as voltage-dependent channel blockers. MCD peptide is also present in the venom of the honey bee Apis mellifera.[3]

Chemistry

MCD peptide is a cationic 22-amino acid residue peptide with two disulfide bridges.[4] Although the MCD peptide sequence shows similarity with apamin,[5] they have different toxic properties. MCD peptide belongs to a large family composed of numerous derivatives detecting specific targets and displaying different toxic effects.[4]

Targets

MCD peptide has immunotoxic as well as neurotoxic properties due to different active sites of the MCD peptide.[6] The MCD peptide has an immunotoxic effect on mast cells [1] by releasing histamine from these cells.[7] MCD peptide has also been described as a potent modulator of voltage-gated ionic channels. It binds to several subclasses of voltage-gated potassium channels (Kv channels), including Kv1.1, Kv1.6, and less potently to Kv1.2.[8][9][10][11] Accordingly, MCD peptide can act in various regions of rat brain, including cerebellum, brainstem, hypothalamus, striatum, midbrain, cortex,[6][12] and hippocampus.[6] However, MCD peptide shows no binding activity in the peripheral neuronal system.[12]

Mode of action

For its immunotoxic properties, a low concentration of MCD peptide can cause mast cell degranulation by releasing histamine; at higher concentrations it displays anti-inflammatory activities.[6]

Through its effect on ionic channels, MCD peptide can induce long term potentiation (LTP) in CA1 region of hippocampus.[13] It binds and inactivates voltage-dependent K+ channels, including fast-inactivating (A-type) and slow-inactivating (delayed rectifier) K+ channels. The binding site of the MCD peptide on the K+ ion channel protein complex is a multimeric protein, consisting of polypeptide chains of molecular weight between 76,000-80,000 and 38,000 Daltons.[14] By blocking potassium channels, the MCD peptide can increase the duration of action potentials and increase neuronal excitability.[6]

Toxicity

The neurotoxicity of MCD peptide is distincted from its histamine releasing function.[2] The histamine releasing function of MCD peptide, at low concentrations, causes the degranulation of mast cell [4] ,[13] and shows anti-inflammatory activity at higher concentrations.[4][15] These actions of MCD peptide on mast cells is thought to be involved in allergic and inflammatory processes related to type I hypersensitivity reaction.[16]

MCD peptide shows neurotoxicity by inducing epileptiform seizures in rat, when intraventricularly injected. This toxicity is caused by the blockage of voltage-gated potassium channels by the MCD peptide.[15] However, there is no toxicity of MCD administered peripherally, even at high doses.[12]

Therapeutic use

As a mast cell activator, the MCD peptide evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses.[17] Therefore, it is used as a vaccine adjuvant. MCD peptide analogs, such as [Ala12] MCD, provide a base for designing agents that can prevent IgE/Fc-RIa interactions and reduce allergic conditions.[18][19]

References

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  2. ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 4.2 4.3 Lua error in package.lua at line 80: module 'strict' not found.
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  6. ↑ 6.0 6.1 6.2 6.3 6.4 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  12. ↑ 12.0 12.1 12.2 Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ 13.0 13.1 Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ 15.0 15.1 Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  18. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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