The amino acid sequence of MCD peptide
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

Peptide

Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

 is a cationic 22-amino acid residue peptide, which is a component of the venom of the bumblebee

Bumblebee

A bumble bee is any member of the bee genus Bombus, in the family Apidae. There are over 250 known species, existing primarily in the Northern Hemisphere although they are common in New Zealand and in the Australian state of Tasmania.Bumble bees are social insects that are characterised by black...

 (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.

Source

MCD peptide is a component of bumblebee

Bumblebee

A bumble bee is any member of the bee genus Bombus, in the family Apidae. There are over 250 known species, existing primarily in the Northern Hemisphere although they are common in New Zealand and in the Australian state of Tasmania.Bumble bees are social insects that are characterised by black...

 (Megabombus pennsylvanicus) venom

Venom

Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...

 . In addition to MCD peptide, melittin

Melittin

Melittin is the principal active component of apitoxin and is a powerful stimulator of phospholipase A2. Melittin is a peptide consisting of 26 amino acids with the sequence GIGAVLKVLTTGLPALISWIKRKRQQ.-Biological effects:...

 and apamin

Apamin

Apamin is an 18 amino acid peptide neurotoxin found in apitoxin . It selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed in the central nervous system and smooth muscle...

 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

Honey bee

Honey bees are a subset of bees in the genus Apis, primarily distinguished by the production and storage of honey and the construction of perennial, colonial nests out of wax. Honey bees are the only extant members of the tribe Apini, all in the genus Apis...

 Apis mellifera .

Chemistry

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

Targets

MCD peptide has immunotoxic as well as neurotoxic properties due to different active sites of the MCD peptide . The MCD peptide has an immunotoxic effect on mast cells  by releasing histamine from these cells . 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  . Accordingly, MCD peptide can act in various regions of rat brain, including cerebellum, brainstem, hypothalamus, striatum, midbrain, cortex , and hippocampus . However, MCD peptide shows no binding activity in the peripheral neuronal system .

Mode of action

For its immunotoxic properties, a low concentration of MCD peptide can cause mast cell degranulation by releasing histamine

Histamine

Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

; at higher concentrations it displays anti-inflammatory activities .

Through its effect on ionic channels, MCD peptide can induce long term potentiation (LTP

LTP

- Science and technology :* Lunar Transient Phenomena, a short-lived change in appearance of Earth's moon* Long-tailed pair, a differential pair amplifier* Lightweight Telephony Protocol, a signaling protocol...

) in CA1 region of hippocampus . 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 . By blocking potassium channels, the MCD peptide can increase the duration of action potentials and increase neuronal excitability .

Toxicity

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

Hypersensitivity

Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...

 reaction .

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 . However there is no toxicity of MCD administered peripherally, even at high doses .

Therapeutic use

As a mast cell activator, the MCD peptide evokes large increases in antigen-specific serum immunoglobulin G

Immunoglobulin G

Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...

 (IgG) responses . 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 .