Melanotropin-Potentiating Factor、促黑素增強因子

Definition

Melanotropin-potentiating factor (MPF) is a C-terminal tetrapeptide of human β-lipotropin, amino acids 88 to 91. It elicits a variety of neurotrophic effects in vivo consistent with its role in neuronal regeneration.

Discovery

Carter et al., in 1979 reported MPF is the C-terminal tetrapeptide of human B-lipotropin 1. Morley et al., in 1981 described MPF analogue with high stability to proteolysis and promote Urodele Limb Regeneration 2, 3.

Structural Characteristics

The structure of MPF has been determined on the bases of chemical and physicochemical examinations which included HPLC, Edman sequence analysis combined analysis of the amino acid composition and FAB-MS analysis 4. MPF is a tetrapeptide (structure Lys-Lys-Gly-Glu) that elicits a variety of neurotrophic effects in vivo consistent with a role in neuronal regeneration 5. The peptide preferably has β-endorphin 31 (Glu or Gin) as the C-terminal amino acid residue. More preferably, the peptide includes or consists of at least β-endorphin 30-31 (Gly-Glu or Gly-Gln), even more preferably β-endorphin 29-31 (Lys-Gly-Glu or Lys-Gly-Gln), and most preferably β-endorphin 28-31 (Lys-Lys-Gly-Glu).

Mode of Action

MPF potentiates the melanotropic activity of melanocyte stimulating hormones. Although the message sequence for the melanotropic and lipolytic activity are identical for β-lipotropin, α- and β-MSH, MPF was not able to affect the lipolytic response to alpha- and beta-MSH in rabbit adipocytes. However, MPF at concentrations of 10-5 and 10-6 mol/l inhibited the lipolytic activity of β-lipotropin. The inhibition of the lipolytic response to β-lipotropin is not connected with the common lipolytic message sequence (β-LPH 47-53). Since β-lipotropin has a second lipolytic sequence in its C-terminal part this second lipolytic core of β-lipotropin might interact with MPF which has no intrinsic lipolytic activity 6.

Functions

Potentiates the melanotropic activity: MPF potentiates the interaction of β-endorphin with its brain opiate receptors. It also potentiates the melanotropic activity of melanocyte-stimulating hormones (MSH) and seems to be involved in other biological systems.

Proliferation of cultured astrocytes: MPF stimulates the proliferation of cultured astrocytes and neurite outgrowth from cultures of neocortical cholinergic and mesenchephalic dopaminergic neurons. The dose-response relationships are biphasic ("bell shaped"), maximal responses being obtained with 10-6 M concentrations of MPF. MPF and nerve growth factor act on different receptors, because their effects on cholinergic neurons are synergistic 5.

Lymphocytes stimulations: Human MPF (Lys-Lys-Gly-Glu) stimulates the proliferative response of human lymphocytes to the T-cell mitogen concanavalin A by 121-751%. Human MPF similarly stimulates rat lymphocytes, but the peak effect is seen at a 100-fold higher dose (10-6 M). Rat MPF (Lys-Lys-Gly-Gln) has a peak effect at 10-6 M with human lymphocytes, but the peak effect with rat lymphocytes is at a 1000-fold lower dose (10-9 M). Truncated forms of the MPFs (Gly-Glu, Gly-Gln, Gly, Glu, Gln) and opioid peptides (β-endorphin, [Leu] and [Met]enkephalin) show insignificant or only weak stimulatory or inhibitory effects. MPF acts via specific non-opioid receptors located on lymphocytes and that endogenously released MPF may have an important role in the functioning of the immune system 7.

Effect on corticosteroid production: Effect of MPF and β-endorphin on corticosteroid production was studied in purified isolated rat adrenal cells. Addition of MPF or β- endorphin, in doses from 5 pg to 5 μg, alone did not result in a corticosterone production. Furthermore, no effect of MPF or β-endorphin in doses from 5 pg to as high as 5 μg for both peptides upon the ACTH or α-MSH-induced corticosteroidogenesis was observed (p greater than 0.1). So both MPF and β-endorphin do not influence the steroidogenic activity in the adrenal gland. Use of these peptides for discrimination of the ACTH/α-MSH receptor interactions is suggested 8.

References

1.Carter RJ, Shuster S, Morley JS (1979). Melanotropin potentiating factor is the C-terminal tetrapeptide of human B-lipotropin. Nature, 279( 5708):74-75.    

2.Morley JS (1981). MPF Analogue with High Stability to Proteolysis. Neuropeptides, 2:109-114.

3.Morley JS, Ensor DM (1989). Structural specificity of beta-endorphin c-terminal tetrapeptide (mpf) in promoting urodele limb regeneration. Life Sciences, 45:1341-1347.

4.Abiko T, Sekino H (1995). Melanotropin-potentiating factor isolated from filtrate of uremic patients suffering from melanosis and carbohydrate intolerance. Amino Acids, 9(3):229-234.

5.Owen DB, Morley JS, Ensor DM, Allen YS, Miles JB (1997). Trophic effects of melanotropin-potentiating factor (MPF) on cultures of cells of the central nervous system. Peptides, 18(7):1015-1021.

6.Richter WO, Schwandt P (1986). Melanotropin potentiating factor inhibits lipolytic activity of beta-lipotropin but not of melanocyte stimulating hormones. Neuropeptides, 7(1):73-77.

7.Owen DL, Morley JS, Ensor DM, Miles JB (1998). The C-terminal tetrapeptide of beta-endorphin (MPF) enhances lymphocyte proliferative responses. Neuropeptides, 32(2):131-139.

8.Goverde HJ, Pesman GJ, Smals AG (1988). The melanotropin potentiating factor and beta-endorphin do not modulate the alpha-melanotropin-or adrenocorticotropin-induced corticosteroidogenesis in purified isolated rat adrenal cells. Neuropeptides, 12(3):125-130.