Biomedical subjects

D H Malin

Publications and source records attributed to D H Malin.

43 records · Page 3Linked to original sources

PubMedDate not supplied

FMRF-NH2-like mammalian octapeptide: possible role in opiate dependence and abstinence.

Yang et al. have isolated from bovine brain an octapeptide, FLFQPQRF-NH2 (F-8-F-NH2), with certain antiopiate properties. Malin et al. previously found that ICV injection of this peptide could precipitate an opiate abstinence syndrome in dependent rats. RIA revealed significantly higher levels of F-8-F-NH2 immunoreactivity in CSF withdrawn from the cisterna magna of morphine-dependent rats as opposed to CSF withdrawn from sham-implanted controls. ICV infusion of IgG from antiserum against F-8-F-NH2 significantly reduced the number of abstinence signs subsequently precipitated by naloxone in morphine-dependent rats.

Animals↗

PubMedDate not supplied

FMRF-NH2-like mammalian peptide precipitates opiate-withdrawal syndrome in the rat.

Yang et al. (14) have isolated from mammalian brain an octapeptide FLFQPQRF-NH2 (F-8-F-NH2) with certain antiopiate properties. Third ventricular injection of 2 micrograms of this peptide together with the aminopeptidase inhibitor bestatin precipitated an opiate-withdrawal syndrome in morphine-dependent but not in nondependent rats. Third ventricular injection in nondependent rats of 15 micrograms of the peptide together with bestatin induced a morphine-withdrawal-like behavioral syndrome. This syndrome was not produced by injection of bestatin or saline vehicle alone and was preventable by injection of 3.5 mg/kg morphine sulphate SC.

Analysis of Variance↗

PubMedDate not supplied

Analog of neuropeptide FF attenuates morphine abstinence syndrome.

The octapeptide FLFQPQRFamide (neuropeptide FF or F8Fa) may play a role in opiate dependence and subsequent abstinence syndrome. Previously, NPFF precipitated opiate abstinence syndrome, while IgG from NPFF antiserum attenuated subsequent naloxone-precipitated abstinence signs in dependent rats. The peptide desamino YFLFQPQRamide (daY8Ra) was synthesized as a possible NPFF antagonist. At a dose of 600 ng ICV, daY8Ra significantly attenuated (p less than 0.001) the number of abstinence-like signs subsequently induced by 10 micrograms NPFF ICV, suggesting that daY8Ra does have antagonist activity against NPFF. Pretreatment of morphine-dependent rats with the same dose of daY8Ra also significantly attenuated (p less than 0.001) the abstinence signs subsequently precipitated by 10 micrograms naloxone ICV. Pretreatment with 600 ng of NPFF itself, or of NPFF modified at the N-terminal only (daY9Fa), failed to attenuate subsequent naloxone-precipitated abstinence, suggesting that the C-terminal modification is critical for NPFF antagonist activity. It should be noted, however, that higher doses of daY8Ra (2 micrograms or more) can precipitate some abstinence signs in a manner similar to NPFF.

Amino Acid Sequence↗

PubMedDate not supplied

Enhanced antiopiate activity in peptidomimetics of FMRFamide containing Z-2,3-methanomethionine.

FMRFa is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. The current study determined the antiopiate potency of FMRFa and two conformationally constrained peptidomimetics of FMRFa containing stereoisomers of Z-2,3-methanomethionine. Morphine abstinence signs were observed after varying doses (0.25-25.0 micrograms) of these substances were injected into the third ventricle of morphine-dependent rats. Although both peptidomimetics were far more potent than FMRFa itself, they bound with lower affinity than FMRFa to rat spinal cord receptors for the mammalian FMRFa-like peptide, NPFF.

Amino Acid Sequence↗

PubMedDate not supplied

Enhanced antiopiate activity and enzyme resistance in peptidomimetics of FMRFamide containing (E)-2,3-methanomethionine.

FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. The current study determined the antiopiate potency of FMRFamide and two conformationally constrained peptidomimetics of FMRFamide containing stereoisomers of (E)-2,3-methanomethionine. Morphine abstinence signs were observed after varying doses (0.25-25.0 microgram) of these substances were injected into the third ventricle of morphine-dependent rats. Both peptidomimetics were far more potent than FMRFamide itself. In addition, although both peptidomimetics bound with lower affinity than FMRFamide to rat spinal cord receptors for NPFF (the mammalian FMRFamide-like peptide), they were far more resistant than FMRFamide to enzymatic degradation by leucine aminopeptidase.

Amino Acid Sequence↗

PubMedDate not supplied

Methanesulfonyl fluoride enhances one-trial reward learning in mid-aged rats.

In previous studies, 18-month-old rats have shown no significant retention 24 hours after the single acquisition trial in a one-trial discriminative reward learning task. In the present study, ten 18-month-old rats pretreated with 0.5 mg/kg MSF IP showed significantly better retention in terms of speed and errors than eleven 18-month-old rats pretreated with injection vehicle alone. However, twelve two-three-month-old rats pretreated with the same dose of MSF failed to show better retention than eleven two-three-month-old rats pretreated with vehicle alone.

Aging↗

PubMedDate not supplied

Chronic methanesulfonyl fluoride enhances one-trial per day reward learning in aged rats.

Aged (24-month-old) rats were treated chronically with methanesulfonyl fluoride (MSF), an acetylcholinesterase (AChE) inhibitor with selectivity for central nervous system AChE, or with injection vehicle alone. Twelve 0.22 mg/kg IP injections were given over 4 weeks. MSF rats showed significantly greater speed and accuracy on a 1 trial/day discriminative reward learning task. The chronic MSF treatment resulted in a 56% decrease in brain AChE activity but no discernable locomotor side effects and no liver damage as indicated by aspartate transferase activity.

Acetylcholinesterase↗