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Biomedical subjects

H Matthies

Publications and source records attributed to H Matthies.

251 records · Page 14Linked to original sources
PubMedDate not supplied

Elimination of granular cells after intrahippocampal colchicine injection causing disappearance of evoked potentials and deterioration of development of the conditioned avoidance reflex in rats.

The aim of our work was to study the involvement, in the process of learning, of synapses between the perforant path and granular cells of the hippocampal dentate fascia for formation of a conditioned reflex (CR) of active avoidance elaborated in response to electrostimulation of the perforant path. To achieve this we used the property of the neurotoxin colchicine at a certain concentration of eliminating selectively the fascia cells. One month after colchicine injection we observed destruction of granular cells, disappearance of the dentate fascia focally evoked potentials, and considerable deterioration in the elaboration of active avoidance CR. Administration of saline solution in control experiments did not bring about such changes. The results obtained show the important role of the entorhinal input into the hippocampus in the learning model used.

Action Potentials↗
PubMedDate not supplied

Effects of deprolorphin, a casomorphin analog, on hippocampal CA1 field potentials in vitro.

The effects of infusion of low concentrations of the synthetic opioid peptide D-Pro4-beta-casomorphin-5(deprolorphin) on electrical field responses in the in vitro hippocampal slice preparation of mice were investigated. Deprolorphin (0.01-10 microM) causes a large enhancement of the population spike (PS) and appearance of additional spikes of CA1 pyramidal cells to Schaffer-commissural stimulation, which were partially antagonized by the opiate receptor antagonist naloxone. It is likely that this analgesic peptide in the hippocampus acts through mu-receptors and neuronal mechanisms already described for morphine and enkephalin analogs.

Animals↗
PubMedDate not supplied

Derivatives of beta-casomorphins with high analgesic potency.

Beta-casomorphin (5) Tyr-Pro-Phe-Pro-Gly, a partial sequence of bovine beta-casein with moderate opioid properties and mu-receptor affinity, was modified by substituting for the natural L-amino acids their D-analogs, and D-pipecolic acid, as well as by amidation of the C-terminal. Substitution of D-Pro or D-pipecolic acid for L-Pro4 considerably increased the analgesic action and the potency on guinea-pig ileum of beta-casomorphin (5) as well as of casomorphin [4] amide. The resulting D-Pro4 analogs Deprolorphin and Deproceptin which showed high analgesic potency after both intracerebroventricular and intravenous administrations. Also, the substitution of D-Phe for L-Phe3 enhanced, even though to a lesser degree, the antinociceptive action. Both naltrexone and naloxone completely blocked the effects in vivo and in vitro. The substitution of D-Pro for L-Pro2 abolished the opioid-like actions, while substituting D-pipecolic acid for L-Pro2 resulted in an increased analgesic effect of remarkably long duration. The correlation of analgesic action with the effects on isolated organs separates the L-Pro4-substituted derivatives and D-Phe3-CM(5) from the other modified casomorphins and morphine, indicating that the analgesic potency of the former was about ten times that of the latter group in the case of identical GPI-potency. This may involve different subpopulations of opiate mu-receptors.

Amino Acid Sequence↗
PubMedDate not supplied

The anticonvulsive effect of BCH 325 is age dependent.

The two different experimental approaches which were applied to study the anticonvulsive effectiveness of BCH 325, a des-tyrosine derivative of bovine beta-casomorphin-(5), in immature (22-day-old) and mature (7-week-old) female rats revealed that the peptide was able to protect mature females from electrically induced seizures and that it had no effect on pentylenetetrazol-induced convulsions. As opposed to this, immature animals were protected against chemically induced seizures but no effect was found using electrically induced seizures.

Age Factors↗
PubMedDate not supplied

Effects of [des-Tyr-D-Phe3]beta-casomorphin (2-5) on sleep pattern in rats.

The effects of the antidepressant-like acting peptide [des-Tyr-D-Phe3]beta-casomorphin(2-5) (Pro-D-Phe-Pro-Gly, BCH-325) on sleep were studied in rats. The rats received subcutaneous injections of BCH-325 in acute experiments (doses: 4, 20, 100, 500 and 2500 nmol/kg) and in a 10-day chronic experiment (50 nmol/kg/day). Acute administration of 20 and 100 nmol/kg enhanced wakefulness, 500 and 2500 nmol/kg enhanced paradoxical sleep, and 4 nmol/kg had no effect. Chronic administration resulted in an increase of paradoxical sleep during the first 5 days of drug treatment. Thus the sleep effects of BCH-325 differ from those of typical antidepressants and other psychotropic drugs.

Animals↗
PubMedDate not supplied

Influence of beta-casomorphin derivatives on chemically and electrically induced seizures.

Derivatives of beta-casomorphin(1-5) at a dose level of 1 mumol/kg body weight were tested for their influence on pentylenetetrazol, picrotoxin, or electrically induced seizures after subcutaneous injection in mice. Tyr-Pro-Phe-D-Pro-Gly was found to facilitate pentylenetetrazol-evoked seizures, whereas desTyr derivatives Pro-Phe-D-Pro-Gly and Pro-Phe-Pyr exhibited anticonvulsant properties against those convulsions. The tripeptide was effective only 10 min after application. The beta-casomorphin derivative Pro-D-Phe-Pro-Gly was effective against electrically induced seizures. The protective action of this tetrapeptide lasted for about 5 h. Additionally, we tested the influence of orally administered Pro-Phe-D-Pro-Gly on pentylenetetrazol-induced seizures and Pro-D-Phe-Pro-Gly on electrically induced seizures. Both peptides were effective at a dose of 5 mumol/kg body weight.

Amino Acid Sequence↗
PubMedDate not supplied

Influence of modified casomorphins on yawning behavior of rats.

Apomorphine-induced yawning was completely suppressed in animals treated with 5 nmol [D-Pro4]casomorphin (CM) (ICV), 10 nmol [D-Phe3]CM (ICV) or 10 nmol [D-Pip4]CM (ICV). The apomorphine-induced yawning was also decreased, by des-Tyr analogs, but only by about 50%. Physostigmine (0.15 mg/kg, IP) induced yawning. The physostigmine-induced yawning was suppressed by 5 nmol [D-Pro4]CM and 10 nmol [D-Phe3]CM. Both [des-Tyr-D-Phe3]CM and [des-Tyr-D-Pip4]CM were without effect, whereas [des-Tyr-D-Pro4]CM increased significantly the physostigmine-induced yawning. The results suggest that dopaminergic transmission can be modulated by beta-casomorphin derivatives, thus resulting in a decrease in yawning. In the case of the des-tyrosine derivatives, we can assume a dopaminergic modulation, too. An increase in serotonergic activity might be supposed for [des-Tyr-D-Pro4]CM.

Amino Acid Sequence↗
PubMedDate not supplied

Biochemical characterization of solubilized muscarinic acetylcholine receptors.

Several in part new methods (salt extraction, phospholipase treatment, transfer to serumlipoproteins, nonionic detergent mixtures) have been extensively examined in order to obtain a solubilized muscarinic acetylcholine receptor with properties suitable for further purification. An optimal mixture of digitonin and gitonin has been found which forms a tightly bound detergent wall around the receptor protein as indicated by ion exchange and monolayer studies and which allows to solubilize the receptor from enriched synaptosomal membranes with a high yield and stability. The specific 3H-QNB binding of this preparation is nearly unchanged between pH 7.5 and 10. The isoelectric point of the muscarinic acetylcholine receptor has been determined by isoelectric focusing to be between pH 4.5 and 4.6.

Acetylcholine↗
PubMedDate not supplied

Enhancement of glutamate release by L-fucose changes effects of glutamate receptor antagonists on long-term potentiation in the rat hippocampus.

In previous studies L-fucose has been shown to facilitate long-term memory formation and to enhance and prolong long-term potentiation (LTP). To search for possible presynaptic or postsynaptic mechanisms that are affected by L-fucose, we examined the effect of L-fucose on (1) inhibition of LTP induction via glutamate receptors by antagonists, (2) paired-pulse facilitation, and (3) presynaptic transmitter release. Coapplication of 0.2 mM L-fucose with the competitive N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovalerate (AP5), or coapplication of 0.2 mM L-fucose in the presence of an inhibitor for class I/II metabotropic glutamate receptors, (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), reversed LTP blockade in the CA1-region of hippocampal slices. In contrast, L-fucose had no effect on the LTP blockade by the noncompetitive NMDA ion-channel blocker (5R,10S)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801). Paired-pulse facilitation, which is a primarily presynaptic phenomenon of short-term plasticity, was decreased in the presence of 0.2 mM L-fucose. Furthermore, L-fucose enhanced the K(+)-stimulated release of [(3)H]-D-aspartate from preloaded hippocampal slices in a concentration-dependent manner. These observations demonstrate an influence of L-fucose on transmitter release that in turn can increase transmitter availability at postsynaptic glutamate receptors. This effect of L-fucose may contribute to the LTP facilitation seen in vitro and in vivo as well as to improvement in memory formation.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

[Switching off of granule cells after intrahippocampal injection of colchicine eliciting the disappearance of evoked potentials and a deterioration in the development of a conditioned avoidance reflex in rats].

The aim of the work was to study the involvement in the process of learning of synapses between the perforant path and granular cells of the hippocampal dentate fascia for formation of conditioned reflex (CR) of active avoidance elaborated in response to electrostimulation of the perforant path. For solving this task, the property was used of the neurotoxin colchicine in a definite concentration to abolish selectively the fascia cells. One month after colchicine injection, destruction of granular cells was observed, disappearance of the dentate fascia focal evoked potentials and considerable deterioration of elaboration of active avoidance CRs. Administration of saline solution in control experiments did not elicit such changes. The obtained results show the decisive role of entorhinal input to the hippocampus in the used learning model.

Animals↗