Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:9083-38-9 (MIF-I)
 50 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels as well as accumulation of serotonin (5-HT) were measured in various brain regions of the rat after administration of alpha-melanocyte-stimulating hormone (MSH) and Pro-Leu-Gly-NH2 (MIF-I). The method used in determining the serotonin measured both 5-OH-tryptamine (5-HT) and 5-methoxytryptamine (5-MT). No statistically significant changes in levels or accumulation of serotonin after pargyline injection were found when unoperated control rats were treated with either MSH or MIF-I. Similar treatment of hypophysectomized rats indicated that both peptides significantly (p less than 0.05) lowered serotonin accumulation only in the area of the frontal cortex; a similar but smaller, not statistically significant, decrease was seen in the hypothalamus and hippocampus of the hypophysectomized rat. Since only hypophysectomized rats were affected, no correlation between the behavioral effects of these peptides (which has been found to occur in both unoperated and hypophysectomized rats) and the biochemical changes could be made.
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PMID:Alpha-MSH and MIF-2 effects on serotonin levels and accumulation in various rat brain areas. 0 14

The effects of MIF-I (Pro-Leu-Gly-NH2) were examined in three experimental conditions in which the opiate antagonist naloxone is active. MIF-I was found to block the analgesic effects of enkephalins and also morphine in the tail-flick test but not in the vas deferens assay. Unlike naloxone, MIF-I did not seem to reduce food intake in VMH-lesioned rats. The results suggest the possibility that MIF-I may represent a class of naturally occurring opiate antagonists with varying activities in independent situations.
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PMID:MIF-I's differential actions as an opiate antagonist. 4 81

A number of questions remain unsettled about the release of melanocyte-stimulating hormone (MSH) and about its function. Even though relatively few investigators are studying this area, some generalities have emerged during the last 10 years. It now seems that release of MSH from the pituitary is inhibited by a substance present in the hypothalamus. The structure of this physiologic inhibitor of MSH release may still not be considered an established entity but there is evidence for additional mechanisms capable of exerting a fine control on the release of MSH. Contrary to some opinions, the release of MSH does not always occur together with the release of ACTH, and the release of the two hormones can be dissociated in several laboratory and clinical situations. In addition, many studies have shown that the pituitary peptide, MSH, exerts behavioral and electroencephalographic effects in both the rat and man. The hypothalamic peptide Pro-Leu-Gly-NH2 (MIF-I) also has direct effects on the central nervous system that may include alleviation of the symptoms of Parkinson's disease.
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PMID:Some questions related to melanocyte-stimulating hormone. 96 14

Melanin was measured in various parts of the rat brain by a spectrophotofluorometric assay. This method could detect natural, Sepia melanin as well as melanin synthesized from L-DOPA. Contrary to published expectations of other investigators, measurable amounts of melanin were found in the brain of albino as well as pigmented rats. The highest concentrations of melanin occurred in the pons-medulla and midbrain, but all regions within the blood-brain barrier contained greater concentrations than samples from many other tissues in the body. No significant change in the melanin content was found after various endocrine manipulations such as removal of the pituitary, pineal, adrenals, thyroid, testes, or ovaries, exposure to constant illumination or darkness, and daily injection for 5 weeks of alpha-MSH, Pro-Leu-Gly-NH2 (MIF-I) or melatonin. As expected, retinal tissue from black-hooded rats contained extremely high levels of melanin whereas that from albino rats contained no melanin. It is thought that the presence of melanin in the brain of albino and pigmented rats may have a function which is still unknown.
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PMID:Melanin in the rat brain. 102 Dec 12

The effect of modified and substituted analogues of prolyl-leucyl-glycinamide (PLG, MIF-I) was investigated on the steady-state level of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in various brain regions. Proline was replaced by D- or L-pipecolic acid (D- or L-Pip), which analogues in turn were protected by benzoxy-carbonyl (Z) group. Substitution by D- or L-pipecolic acid caused opposite changes in the DA level of the dorsal hippocampus. These effects were absent it the N-terminal of either analogues was protected by Z-group. Following the above mentioned N-terminal modification, the amino group of the C-terminal glycine was also substituted by methyl-esther (Gly-OMe), Z-D-Pip-Leu-Gly-OMe decreased the mesencephalic DA level, while Z-L-Pip-Leu-Gly-OMe increased the 5-HT content of the mesencephalon and striatum. In general, N-terminal substitution by D-pipecolic acid decreased, whereas that by L-pipecolic acid increased the monoamine level in the brain.
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PMID:Effect on brain monoamines in the rat of substituted and protected analogues of the oxytocin fragment, prolyl-leucyl-glycinamide following N-terminal substitution by D- and L-pipecolic acid. 287 93

Neurotensin (NT), an endogenous tridecapeptide, produces significant hypothermia after intracisternal (i.c.) or intracerebroventricular (i.c.v.) administration in microgram quantities in a variety of laboratory animals. The present study sought to clarify the mechanism of the hypothermic action by utilizing pharmacological treatments which alter the function of brain neurotransmitter systems. Pretreatment of rats with anti-muscarinic (atropine), anti-noradrenergic (propranolol, a beta-blocker; phenoxybenzamine, an alpha-blocker) or anti-opiate (naloxone) agents did not significantly alter NT-induced hypothermia. Similarly depletion of brain serotonin (5-HT) with parachlorophenylalanine did not affect NT-induced hypothermia. However, depletion of brain catecholamine content with 6-hydroxydopamine resulted in a significant potentiation of NT-induced hypothermia as did pretreatment with haloperidol, a dopamine (DA) receptor antagonist. Furthermore, in rats with selective depletions of brain DA, but not norepinephrine (NE), NT-induced hypothermia was significantly augmented. Thus an interaction between brain DA systems and NT appears likely. These data indicate that NT-induced hypothermia is not dependent on intact functional activity of NE, 5-HT, muscarinic ACh or endogenous opiate systems but suggests interactions between brain DA circuits and NT. In other experiments, NT-induced hypothermia was found to be antagonized significantly by i.c. injection of thyrotropin-releasing hormone (TRH), but not by pretreatment with L-triiodothyronine. Another endogenous tripeptide (Pro--Leu--Gly--NH2, MIF-I) had no effect. Thyroidectomy (THX) significantly potentiated NT-induced hypothermia; NT administered i.c. significantly reduced the high serum TSH levels of THX rats. Thus, NT and TRH, two endogenous peptides, appear to be antagonists in certain systems.
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PMID:Neurotensin-induced hypothermia: evidence for an interaction with dopaminergic systems and the hypothalamic--pituitary--thyroid axis. 644 51

An aminopeptidase preferentially hydrolyzing Leu- or Ala-Gly-Gly was purified from rat brain cytosol and detailed studies have been performed on its substrate specificity and the effects of inhibitors. The enzyme was devoid of di- and oligopeptidase contamination. Biologically active tripeptides such as Met-Leu-Tyr (chemotactic factor), Gly-His-Lys (liver growth factor) and Thr-Val-leu central nervous system tripeptide) were hydrolyzed at rates 0.05-0.15-times that of Leu-Gly-Gly. Melanostatin (Pro-Leu-GlyNH2) did not serve as a substrate. Substrates bearing N-terminal charged groups, or ones with proline in positions 2 or 3, or those with D-amino acid in positions 1 or 2, or with C-terminal CONH2, were poorly hydrolyzed or did not act as substrates, providing information on subsites involved in enzyme catalysis. The enzyme was inhibited competitively by bestatin (Ki 10-7 M) and by Captopril (2.5.10-7 M, D-3-thio-2-methylpropanyl proline) and by low concentrations of Zn2+ or PCMB, and at higher concentrations by TPCK and PMSF. Inhibition was observed for the chemotactic factor (I50 13 microM) and for the central nervous system tripeptide (195 microM). The enhanced action of Captopril was attributed to the presence of the -SH and -CH3 groups, since inhibition was shared by di- and tripeptides with proline in positions 2 and 3. The specificity pattern of brain enzyme was different from that reported for kidney and intestine.
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PMID:A highly specific aminotripeptidase of rat brain cytosol. Substrate specificity and effects of inhibitors. 712 1

Intracellular recording was used to study the effects of eight opioid tetrapeptides with similar amino acid sequences, namely endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), morphiceptin (Tyr-Pro-Phe-Pro-NH2), hemorphin-4 (Tyr-Pro-Trp-Thr), Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2), TAPS (Tyr-D-Arg-Phe-Sar) and DALDA (Tyr-D-Arg-Phe-Lys-NH2), on neurons of the rat locus coeruleus, using a submerged brain slice preparation. All the tetrapeptides inhibited the spontaneous firing of all neurons of the locus coeruleus tested. Higher concentrations also caused hyperpolarization of the neurons and a reduction in input resistance. These inhibitory effects were rapidly and completely reversed by CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, a selective micro-opioid receptor antagonist). The IC50 of the opioid tetrapeptides, in terms of inhibition of spontaneous firing of locus coeruleus neurons, as compared to the concentrations which produced a 5-mV hyperpolarization (HC5 mV) were calculated, giving the same rank order of potency: TAPS (IC50 = 1.9 nM, HC5 mV = 3.4 nM) > endomorphin-1 (IC50 = 8.8 nM, HC5 mV = 22.1 nM) and endomorphin-2 (IC50 = 5.3 nM, HC5 mV = 16.1 nM)> DALDA (IC50 = 20 nM, HC5 mV = 143 nM) > morphiceptin (IC50 = 65 nM, HC5 mV = 335 nM) > Tyr-W-MIF-I (IC50 = 3.8 microM, HC5 mV = 6.7 microM) > hemorphin-4 (IC50 = 6.7 microM, HC5 mV = 36.9 microM) > Tyr-MIF-1 (IC50 = 37.5 microM, HC5 mV = 76.2 microM). Comparison of the ability of endomorphin-1 and endomorphin-2 to inhibit spontaneous firing based on single-cell recordings (n = 5) showed these two peptides to be equipotent. Based on these results, the structure-activity relationships of these opioid tetrapeptides are discussed herein.
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PMID:Structure-activity relationships of naturally occurring and synthetic opioid tetrapeptides acting on locus coeruleus neurons. 1039 16