Melanocyte-Stimulating Hormone-Release Inhibiting Factor (MIF-I) and Analogs
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Melanocyte-Stimulating Hormone-Release Inhibiting Factor (MIF-I) and Analogs
A hypothalamic tripeptide
, enzymatic degradation product of oxytocin, that inhibits the release of Melanocyte-Stimulating Hormone.
Discovery
Marks et al., reported ubiquitous enzyme melanocytc-stimulating hormone release-inhibiting factor (MIF) 1,2. Later William H et al., in 1973 reported the hydrolysis of MIF by a Mn2 -stimulated aminopeptidase of molecular weight 11.7 kDa that cleaves a wide variety of tripeptides and the dipeptide, Leu-Gly 3.
Structural Characteristics
William H et al., had used several procedures to isolate the tetrapeptide Tyr- Pro-Leu-Gly-NH2 frombo vine hypothalamus 3. This brain enzyme MIF-I, has physical and enzymic properties distinctly different from rat brain arylamidase. Two Mn2 inhibited bovine brain aminopeptidases, which cleave Leu-Gly-Gly in common with the Mn2 stimulated aminopeptidase, were inactive toward all the peptide hormones tested, including melanocyte-stimulating hormone release inhibiting factor. These brain peptidases capable of acting upon the peptide hormones exhibit a very high degree of substrate specificity 3.
Mode of Action
The pituitary-hypothalamo-pineal complex involving MIF-I and melatonin has been strongly emphasized in the adaptive mechanism of the animal. A series of experiments were conducted to investigate the effects of MIF-I and melatonin on novelty-induced defecation, step-down activity, plasma 11-OHCS levels and whole brain DA and NE concentrations over days of novelty X drug treatment. MIF-I significantly habituated novelty-induced defecation and increased brain norepinephrine (NE) and dopamine (DA) levels over 5 days of drug X novelty treatment. MIF-I did not show any significant effect on the step-down activity of the rats. The results suggest that central catecholamines may be implicated in the behavioral changes observed after MIF-I administration and in the interaction of the pituitary-hypothalamo-pineal complex involving MSH, MIF-I and melatonin 4.
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