3D model (JSmol)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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The principal function of melittin as a component of bee venom is to cause pain and destruction of tissue of intruders that threaten bees hive. However in honey bees, melittin is not only expressed in the venom gland, but also in other tissues when infected with pathogens. The two venom molecules, melittin and secapin, are over-expressed in honey bees infected with various pathogens, possibly indicating a role for melittin in the immune response of bees to infectious diseases.
Melittin is a small peptide with no disulfide bridge; the N-terminal part of the molecule is predominantly hydrophobic and the C-terminal part is hydrophilic and strongly basic. In water, it forms a tetramer but it also can spontaneously integrate itself into cell membranes.
Mechanism of action
Injection of melittin into animals and humans causes pain sensation. It has strong surface effects on cell membranes causing pore-formation in epithelial cells and the destruction of red blood cells. Melittin also activates nociceptor (pain receptor) cells through a variety of mechanisms.
Melittin can open thermal nociceptor TRPV1 channels via cyclooxygenase metabolites resulting in depolarization of nociceptor cells. The pore forming effects in cells causes the release of pro-inflammatory cytokines. It also activates G-protein-coupled receptor-mediated opening of transient receptor potential channels. Finally melittin up-regulates the expression of Nav1.8 and Nav1.9 sodium channels in nociceptor cell causing long term action potential firing and pain sensation.
Melittin inhibits protein kinase C, Ca2+/calmodulin-dependent protein kinase II, myosin light chain kinase, and Na+/K+-ATPase (synaptosomal membrane). Mellitin blocks transport pumps such as the Na+-K+-ATPase and the H+-K+-ATPase. In vitro, melittin increases the permeability of cell membranes to ions, particularly Na+ and indirectly Ca2+, because of the Na+-Ca2+-exchange. This effect results in morphological and functional changes, particularly in excitable tissues.
Potential medical applications
Bee venom therapy has been used as a traditional medicine for the treatment of pain, inflammatory diseases, and of cancer. This has motivated research into the use of the main active component of bee venom, melittin, to treat these same diseases. However the non-specific toxicity of melittin has severely limited its clinical application. While melittin has been studied in in vitro and animal models for the treatment of inflammation and cancer, human efficacy data is lacking.
- Melitten – Compound Summary, PubChem.
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