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Biomedical subjects

D de Wied

Publications and source records attributed to D de Wied.

At least 127 records · Page 7Linked to original sources

Selective conversion of beta-endorphin into peptides related to gamma- and alpha-endorphin.

beta-Endorphin (beta-LPH61-91) is a well known endogenous opioid ligand. It and related peptides have recently been implicated in the control of adaptive behaviour. Smaller beta-endorphin fragments appeared to be more active moieties than the parent molecule in a number of behavioural situations. Their effects seemed to occur independently of interaction with opiate receptor sites in the brain. Moreover, elimination of the opiate-like properties of gamma-endorphin (beta-LPH61-77) by removing the N-terminal amino acid yielded des-tyrosine-gamma-endorphin (beta-LPH62-77, dT gamma E) which had greater behavioural activity than gamma-endorphin. The CNS effects of dT gamma E resembled those of neuroleptic drugs in several test systems. alpha-Endorphin (beta-LPH61-76) exerted effects opposite to those of dT gamma E and in some aspects its activity was comparable to that of psychostimulant drugs. This opposition of effects suggests that a balance between gamma- and alpha-type endorphins is involved in the control of brain function. We report here that either gamma-endorphin and dT gamma E or alpha-endorphin and des-tyrosine-alpha-endorphin (beta-LPH62-76, DT alpha E) can be formed preferentially from beta-endorphin by enzymes associated with an enriched synaptosomal plasma membrane fraction from brain. It is suggested that these enzymes have a role in brain homeostatic mechanisms by regulating the generation of these substances.

Animals↗

Sexual dimorphism in passive avoidance behavior of rats: relation to body weight, age, shock intensity and retention interval.

Female rats were inferior to age- and weight-matched males in the retention of a step-through type passive avoidance response 24 and 48 hr after the learning. This sex difference could be observed at different intensities of foot shock which was used as aversive stimulus during the single learning trial. Additionally, unlike in males, retention of the passive avoidance response in the females was not the function of shock intensity. Male and female rats, however, showed similar passive avoidance if tested immediately after the learning trial. The results suggest the existence of sexual dimorphism in memory processes.

Age Factors↗

Effect of oxytocin and vasopressin on memory consolidation: sites of action and catecholaminergic correlates after local microinjection into limbic-midbrain structures.

The effects of local postlearning microinjections of arginine-vasopressin (AVP) and oxytocin (OXT) on one-trial learning passive avoidance behavior and the influence of AVP on alpha-MPT-induced disappearance of norepinephrine (NE) and dopamine (DA) in discrete brain regions have been studied in the rat. OXT injected bilaterally in the hippocampal dentate gyrus (25-25 pg) or in the midbrain dorsal raphe nucleus (50 pg) significantly attenuated passive avoidance behavior. Facilitation of passive avoidance behavior was observed when the peptide was injected into the dorsal septal nucleus. AVP facilitated passive avoidance behavior when administered into the hippocampal dentate gyrus, dorsal raphe nucleus or dorsal septal nucleus. Injection of either neuropeptides into the central amygdaloid nucleus appeared to be ineffective. One week after the behavioral experiments a repeated injection of AVP into the hippocampal dentate gyrus increased the disappearance of NE in the dentate gyrus and in the nucleus ruber. An injection into the dorsal septal nuclei decreased the NE disappearance in the dorsal septal nucleus itself and increased it in the nucleus ruber. Injection in the dorsal raphe nucleus led to an increase in the disappearance of DA in the locus coeruleus and in the nucleus ruber. It is concluded that memory consolidation can be oppositely influenced by local application of minute amounts of either OXT or AVP into certain limbic-midbrain structures, suggesting an involvement of these brain regions in the memory effects of these peptides. Modulation of catecholamine turnover in specific brain areas after AVP administration may be related to this behavioral effect.

Animals↗

Improvement of schizophrenic patients treated with [des-Tyr1]-gamma-endorphin (DTgammaE).

It was postulated from animal experiments that gamma-endorphin and, in particular, the nonopiate-like peptide [des-Tyr1]-gamma-endorphin (DTgammaE, beta-lipotropin [beta-LPH]62-77) have neurolepic-like activity. To test this, 14 patients with long-lasting, relapsing schizophrenic or schizoaffective psychosis resistant to conventional neuroleptics were treated with DTgammaE. An open design was used first for six patients (study 1) and a double-blind, crossover design for the other eight (study 2). In study 1, all neuroleptic medication was discontinued and 1 mg of DTgammaE zinc phosphate was given daily intramuscularly for about seven days. In study 2, six patients were maintained with neuroleptic therapy and two patients were drug free; all eight received daily intramuscular injections of 1 mg of nonlasting DTgammaE in saline and solution for eight days. There was transient or semipermanent improvement in both studies in which the psychotic symptoms diminished or even disappeared. In study 2, there was a slight but significant improvement with the first treatment. Improvement continued and by day 4, the psychotic symptoms had almost disappeared. No toxic side effects were noted. These effects of DTgammaE may be a consequence of the normalization of beta-endorphin homeostasis in the brain.

Adult↗

Pituitary-brain transport of neurotensin: functional significance of retrograde transport.

The ability of the peptide neurotensin (NT) to affect central nervous system function after pituitary-brain transport was examined in adult male rats. Animals were anesthetized and maintained under ether and their pituitaries were exposed by the pharyngeal route. They were then given NT or physiological saline solution by various routes of administration, and colonic temperature (CT) was monitored over a 2-h period. Animals given intracerebroventricular injections of 10 micro g NT showed significantly lower colonic temperatures over the 2-h-measurement period compared to rats injected intraventricularly with the solvent vehicle (0.15 M NaCl). Intrapituitary injection of 10 or 50 micro g NT also markedly decreased CT in a dose-related manner compared to rats given similar injections of the solvent vehicle. Section of the pituitary stalk 24 h before injection of 50 micro g NT into the pituitary totally abolished the hypothermic effect of the peptide. NT in a dose of 50 micro g did not significantly modify CT when injected either iv or into the space between the pituitary and the dura compared to animals given the solvent vehicle. The results suggest that peptides may undergo retrograde transport from the pituitary to appropriate sites in the central nervous system and retain their ability to affect brain function.

Animals↗

Neurohypophyseal principles and memory.

The neurohypophyseal hormones vasopressin and oxytocin modulate memory processes. Vasopressin facilitates, while oxytocin attenuates memory consolidation and retrieval. These influences are located in different regions of the molecules. Thus, the neurohypophyseal hormones act as precursor molecules for neuropeptides involved in memory processes. The covalent ring structures of both vasopressin and oxytocin mainly affect consolidation; the linear parts, retrieval processes; while nearly the whole oxytocin or vasotocin molecule is needed for attenuation of consolidation and retrieval. Regional studies, utilizing microdissection techniques in combination with a sensitive radioenzymatic catecholamine assay, revealed a distinct pattern of effects on cerebral alpha-methyl-p-tyrosine methylester-induced catecholamine disappearance following intraventricular vasopressin administration in limbic midbrain structures. In situations in which the amount of bioavailable vasopressin in the brain is absent, as is the case in the Brattleboro rat with hereditary diabetes insipidus, or neutralized in normal Wistar rats following the intraventricular administration of antivasopressin serum, regional catecholamine disappearance in most cases is altered in a direction opposite to that observed after intracerebroventricular vasopressin administration. These results indicate that vasopressin modulates memory processes by modulation of neurotransmission in distinct catecholamine systems. Recent experiments suggest that the influence of vasopressin on memory consolidation is mediated by the dorsal noradrenergic bundle via terminal regions of this bundle.

Amnesia↗