Chronic administration of 1-prolyl-l-leucyl-glycinamide (MIF-I) to mice slightly reduced morphine's antinociceptive activity in the hot-plate test and modified the biphasic motor activity response to morphine. MIF-I antagonized the initial depression of activity and potentiated the increased motor activity phase. Chronic treatment of rats with MIF-I prevented morphine's antinociceptive activity in the tail flick tests. MIF-I partly antagonized the inhibition by morphine of the coaxially stimulated guinea-pig ileum preparation. The inhibition of the ileum produced by ethylketocyclazocine was weakly antagonized by MIF-I. In contrast, MIF-I had no effect on the inhibition of the stimulated mouse vas deferens produced by Leu-enkephalin. The findings show that MIF-I weakly and selectively inhibits mu-type opiate receptors which suggests that MIF-I could be an endogenous inhibitor of opiate receptors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/0196-9781(80)90006-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
"Near Cure" treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct.
Cell Immunol
August 2022
Neuroimmunology Research, R&D-31, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd, Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA; Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
Our previous studies demonstrated increased serum levels of macrophage migration inhibitory factor (MIF-1) and its homologue, MIF-2, in males during MS progression; and that genetically high-MIF-expressing male subjects with relapsing multiple sclerosis (MS) had a significantly greater risk of conversion to progressive MS than lower-MIF-expressing males and females. However, female MS subjects with severe disease expressed higher levels of CD74, the common MIF-1/MIF-2 receptor, on blood cells. In the murine model of MS, experimental autoimmune encephalomyelitis (EAE), both male and female mice lacking MIF-1 and/or MIF-2 were clinically improved during development of moderately severe disease, thus implicating both homologs as co-pathogenic contributors.
View Article and Find Full Text PDFDiscovery of New Potent Positive Allosteric Modulators of Dopamine D Receptors: Insights into the Bioisosteric Replacement of Proline to 3-Furoic Acid in the Melanostatin Neuropeptide.
J Med Chem
May 2021
LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
The control of Parkinson's disease (PD) is challenged by the motor and non-motor fluctuations as well as dyskinesias associated with levodopa long-term therapy. As such, pharmacological alternatives to reduce the reliance on this drug are needed. Melanostatin (MIF-1), a positive allosteric modulator (PAM) of D receptors (DR), is being explored as a novel pharmacological approach focused on DR potentiation.
View Article and Find Full Text PDFSynthesis, Pharmacological, and Biological Evaluation of 2-Furoyl-Based MIF-1 Peptidomimetics and the Development of a General-Purpose Model for Allosteric Modulators (ALLOPTML).
ACS Chem Neurosci
January 2021
Dept. of Organic Chemistry II, University of Basque Country (UPV-EHU), 48940 Leioa, Spain.
This work describes the synthesis and pharmacological evaluation of 2-furoyl-based Melanostatin (MIF-1) peptidomimetics as dopamine D modulating agents. Eight novel peptidomimetics were tested for their ability to enhance the maximal effect of tritiated -propylapomorphine ([H]-NPA) at D receptors (DR). In this series, 2-furoyl-l-leucylglycinamide () produced a statistically significant increase in the maximal [H]-NPA response at 10 pM (11 ± 1%), comparable to the effect of MIF-1 (18 ± 9%) at the same concentration.
View Article and Find Full Text PDFThe Effect of PAOPA, a Novel Allosteric Modulator of Dopamine D2 Receptors, on Signaling Proteins Following Sub-Chronic Administration in Rats.
Curr Mol Pharmacol
October 2021
Department of Psychiatry and Behavioral Neurosciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Background: Allosteric modulators of G-protein coupled receptors regulate receptor activity by binding to sites other than the active site and have emerged as a new and highly desirable class of drugs. PAOPA (3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide), a peptidomimetic analog of L-prolyl-L-leucyl-glycinamide, is a potent dopamine D2 receptor allosteric modulator. PAOPA has shown therapeutic effects in pre-clinical models of schizophrenia and extrapyramidal dysfunction.
View Article and Find Full Text PDFEvaluating macrophage migration inhibitory factor 1 expression as a prognostic biomarker in colon cancer.
Tumour Biol
June 2020
Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
Objective: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker.
Methods: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I-IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase-polymerase chain reaction.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!