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Biomedical subjects

D de Wied

Publications and source records attributed to D de Wied.

At least 91 records · Page 5Linked to original sources
PubMed1984

Clinical, biochemical, and hormonal aspects of treatment with Des-tyr1-gamma-endorphin in schizophrenia.

Des-tyr1-gamma-endorphin (DT gamma E) was administered intramuscularly in a dose of 1 mg/day for 10 days to 18 neuroleptic-free schizophrenic patients in a double-blind crossover design. Six patients showed either a slight or no antipsychotic response; seven patients showed a moderate antipsychotic response; and the remaining five patients showed a marked antipsychotic response. DT gamma E led to a decrease of plasma prolactin levels in patients treated with DT gamma E in the first period of experimental treatment as compared to those treated with placebo. Neither plasma levels of growth hormone and cortisol nor cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylglycol were affected by DT gamma E. Patients suffering from a hebephrenic or paranoid type of schizophrenia and those presenting relatively fewer negative symptoms were most susceptible to treatment with DT gamma E. These data confirm and extend previous findings that DT gamma E has antipsychotic properties in a number of schizophrenic patients.

Adolescent↗
PubMed1984

Ceruletide resembles antipsychotics in rats and schizophrenic patients. Preliminary report.

Peptides related to the C-terminal part of cholecystokinin, including ceruletide, were found to be active in a number of behavioral test procedures in rats, predicting antipsychotic action. In a subsequent clinical trial ceruletide was administered intramuscularly in a dose of 40 micrograms twice for 2 consecutive weeks to 6 neuroleptic-treated schizophrenic patients following a single-blind design. In 3 patients, a pronounced long-lasting antipsychotic effect was observed, while in the other 3 the response was less marked. It is suggested that ceruletide may be a potential antipsychotic peptide.

Animals↗
PubMed1984

The stimulatory effect of a non-opiate beta-endorphin fragment on arginine-vasopressin release in rats.

The effect of the non-opiate beta-endorphin (beta E) fragment 2-9 and related peptides on immunoreactive (IR) arginine8 -vasopressin (AVP) levels was studied in the rat eye plexus plasma. Additionally, the effect of beta E 2-9 on AVP release from pituitary neurointermediate lobes ( NILs ), in vitro was studied. IR AVP levels in the eye plexus plasma increased after subcutaneous (s.c.) injection of beta E 2-9. In female rats peak values were observed 2 min after the administration of beta E 2-9 (10 micrograms/rat). Male rats were 100 times more sensitive than female rats. A dose-response study revealed a U-shaped relationship for this effect of beta E 2-9 in animals of both sexes. From structure-activity studies it appeared that beta E 2-9 was the most effective fragment. Intracerebroventricular (i.c.v.) administration of beta E 2-9 did not affect the IR-AVP levels in eye plexus plasma. Moreover, AVP release from the rat NILs cells in vitro was stimulated by perfusion with beta E 2-9, indicating a direct effect of the peptide on the pituitary. Therefore we suggest that beta E 2-9 increases AVP release by a direct action on the posterior pituitary.

Animals↗
PubMed1983

A major metabolite of arginine vasopressin in the brain is a highly potent neuropeptide.

A peptide that accumulated as the major product during the proteolysis of arginine vasopressin by rat brain synaptic membranes was isolated and its structure was shown to be the hexapeptide pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2. When administered intracerebroventricularly in extremely low doses, this vasopressin fragment and its desglycinamide derivative facilitated memory consolidation in a passive avoidance situation. These vasopressin metabolites, which are devoid of pressor activity, constitute highly potent neuropeptides with selective effects on memory and related processes; they are activated via proteolytic processing of vasopressin by brain peptidases.

Amino Acid Sequence↗
PubMed1983

Differential responses in immunoreactive arginine-vasopressin content of microdissected brain regions during passive avoidance behavior.

Immunoreactive arginine-vasopressin (IR-AVP) was measured in various hypothalamic and extrahypothalamic nuclei of male Wistar rats immediately after the 24 h retention test of a passive avoidance response. IR-AVP concentrations in paraventricular, suprachiasmatic and lateral septal nuclei were significantly decreased in comparison with the non-shocked rats, while IR-AVP was increased in the central amygdala nucleus, subfornical organ and locus coeruleus. No significant differences in IR-AVP levels were found in the habenular and periventricular hypothalamic nucleus, organum vasculosum of lamina terminalis and medial and dorsal raphe nucleus.

Animals↗
PubMed1983

The blood pressure changes resulting from the microinjection of fragments of the beta endorphin molecule into the nucleus tractus solitarii (NTS).

Unilateral microinjection of gamma endorphin (1-17) into the nucleus tractus solitarii (NTS) of the urethane anaesthetised rat produces a dose-related pressor response. This effect has been examined in the present study, by means of fragments of the molecule. Unilateral application of the peptides 6-16, 10-16, 6-17 and 10-17 (1 ng) all produced an equivalent rise in blood pressure, however the time course of 6-16 and 10-16 was more rapid than that of gamma endorphin or the fragments containing the 17th amino acid. Naloxone (10 ng) administered into the NTS, did not affect the maximum rise in pressure induced by 6-17 (1 ng). It is concluded that in addition to a depressor region, which is dependent on the N-terminal tyrosine, the beta endorphin molecule (1-31) also has a pressor region, which is present within the amino acid sequence 10-16, and is a non-opiate effect.

Animals↗
PubMed1983

Comparative effects of ACTH-related peptides on acquisition of shuttle-box avoidance behavior of hypophysectomized rats.

Hypophysectomy resulted in a marked impaired acquisition of shuttle-box avoidance learning, when lower shock intensity (0.05 mA) was used as the unconditioned stimulus, but not when shock intensity was increased to 0.12 mA. Daily subcutaneous treatment with ACTH4-10 (6 micrograms/day), ACTH4-7 (6 micrograms/day), [Met(O2)4]ACTH4-7 (2 micrograms/day), ACTH4-9 analog (Org 2766) (60 ng/day), and an ACTH4-16 analog (HP 953 A) (60 ng/day) for 7 days normalized avoidance acquisition of hypophysectomized rats during the treatment period. The beneficial effect of the peptides was of a short-term nature, since it disappeared after discontinuation of the treatment. Microgram amounts of Org 2766 did not influence acquisition of hypophysectomized rats. [D-Phe7]ACTH4-10 (60 micrograms/day) further reduced the already deficient acquisition of avoidance behavior of hypophysectomized rats. This latter effect may be due to an antagonistic effect towards brain-borne ACTH-related peptides. ACTH1-16 -NH2 antiserum administered intracerebroventricularly 30 min prior to a massed-trial shuttle-box acquisition session reduced avoidance acquisition in hypophysectomized rats. This suggests that in addition to ACTH and related peptides from the pituitary, brain-borne ACTH-like peptides are involved in avoidance learning.

Adrenocorticotropic Hormone↗
PubMed1983

Effects of desglycinamide-arginine-vasopressin (DG-AVP) on memory processes in diabetes insipidus patients and non-diabetic subjects.

The effects of desglycinamide9-arginine8-vasopressin (DG-AVP) on memory processes have been studied in patients with central diabetes insipidus (DI) and in non-diabetic control patients. Acute im injection of DG-AVP improved some aspects of short-term memory. Subchronic intranasal administration of DG-AVP facilitated short-term memory more consistently and in addition improved long-term memory. DG-AVP increased the attention, but only in the non-diabetic subjects. The effects of DG-AVP on memory processes persisted after discontinuation of treatment. DG-AVP did not affect the parameters for water and electrolyte metabolism, blood pressure and pulse rate neither in DI nor in the control patients. Thus, the memory effects of DG-AVP are probably mediated by a direct action on the central nervous system.

Adolescent↗
PubMed1983

Pituitary and hypothalamic hormones as precursor molecules of neuropeptides.

The behaviorally active meiety of ACTH resides in only a few amino acid residues and is independent of its peripheral endocrine effects. Although pituitary hormones may reach the brain through the circulation and by retrograde transport through the portal vessel system, the recent discovery that ACTH as part of a big precursor molecule, pro-opiomelanocortin, is widely distributed throughout the brain suggests that "brain borne" ACTH may be the main supplier of behaviorally active neuropeptides. The biotransformation of pro-opiomelanocortin in the anterior pituitary differs from that in the intermediate/posterior lobe and the brain. Thus, the biotransformation of hormones at the site of release may determine their ultimate function i.e. as a hormone (pituitary) or as a neuropeptide (brain). Structure activity studies, and studies on the biotransformation of ACTH in brain synaptosomes corroborate the hypothesis that ACTH in the brain is a precursor of the second order of neuropeptides involved in adaptive behavior. A great number of studies in a variety of behavioral paradigms has shown that ACTH neuropeptides are involved in (visual) attention and motivation, vigilance and learning and maintenance behavior. Other pro-opiomelanocortin molecules such as beta-endorphin undergo a similar processing. Structure activity studies and biotransformation studies of this hormone have revealed the generation of neuropeptides with neuroleptic-like and psychostimulant properties. The neurohypophyseal hormones vasopressin and oxytocin appear to function as precursor molecules of the second order of potent neuropeptides involved in memory processes. The same may hold for other "brain borne" hormones.

Adrenocorticotropic Hormone↗
PubMed1982

Electroencephalographic changes in the lateral septum complex following systemic administration of des-Tyr1 -alpha-endorphin, des-Tyr1-gamma-endorphin and haloperidol in rats.

The influence of systemically administered Des-Tyr1-alpha-endorphin (DT alpha E), Des-Tyr1-gamma-endorphin (DT gamma E) and haloperidol on electroencephalographic (EEG) activity of the lateral septum complex (LSC) and the frontal cortex was studied in male rats. DT alpha E (2 micrograms) significantly increased whereas DT gamma E (10 micrograms) significantly decreased the amounts of activity in the 5 Hz band. In addition, DT alpha E promoted production of 15-20 Hz activity, while DT gamma E decreased the amount of 20-30 Hz activity. EEG activity exhibited a marked variability which persisted throughout the recording session following administration of the peptides. Haloperidol markedly decreased the proportion of 10-15 Hz activity. The alterations in EEG of the frontal cortex were similar to those in LSC but less pronounced. The differences in the time course and frequency bands affected suggest that the effects of peptides and haloperidol on EEG activity of LSC are not mediated by the same mechanisms.

Animals↗
PubMed1982

Neuropeptides, mental performance and aging.

The presence of peptidergic neuronal networks in the brain and the modulating action of neuropeptides on brain functions as evidenced by their behavioral influence in particular support the concept that the brain like the peripheral endocrine glands is an endocrine target organ which is as sensitive to treatment with neuropeptides as the peripheral glands are to pituitary hormones. Animal and human data are reviewed showing that neuropeptides related to ACTH/MSH affect motivational and attentional processes and that those related to vasopressin are involved in memory processes. Since these functions decline during aging it is postulated that a decreased bioavailability of neuropeptides in brain of elderly people is associated with specific disturbances in mental performance. Thus, the decreased mental ability of the aged may be restored by treatment with neuropeptides particularly those with little, if any, peripheral, endocrine activity, like the ACTH neuropeptide Org 2766 and the vasopressin neuropeptide DGAVP.

Adrenocorticotropic Hormone↗
PubMed1982

An inhibitory role of beta-endorphin in central cardiovascular regulation.

The cardiovascular effects of beta-endorphin after administration directly into the nucleus tractus solitarii (NTS) of urethane anaesthetised rats were investigated. Unilateral injection resulted in a dose related fall in mean arterial pressure and heart rate. No change in respiratory frequency was prevented and the bradycardia reduced by pretreatment with locally applied naloxone (10 ng). This dose of the opiate antagonist had no effect on mean arterial pressure or heart rate when administered alone. Antiserum to beta-endorphin (1:50 dilution) caused a rise in pressure and a tendency towards tachycardia on injection into the NTS, while it completely blocked the depressor response and bradycardia induced by beta-endorphin. These results are consistent with the view that a beta-endorphin-like peptide has a depressor role in the central nervous system. The hypotension may result from an effect within the central connections of the baroreceptor reflex arc, probably at the level of the NTS.

Animals↗
PubMed1982

Effect of des-Tyr1-gamma-endorphin and des-Tyr1-alpha-endorphin on alpha-MPT-induced catecholamine disappearance in rat brain nuclei: a dose--response study.

The effect of des-Tyr1-gamma-endorphin (beta-LPH62-77, DT gamma E) and des-Tyr1-alpha-endorphin (beta-LPH62-76, DT alpha E), administered intracerebroventricularly (icv) in doses of 0.01, 0.1, 1 and 10 micrograms, was studied on the alpha-methyl-p-tyrosine-(alpha-MPT) induced disappearance of catecholamines in a number of microdissected rat brain regions, which were selected on the basis of the neuroanatomy of the dopamine systems in the brain and of previous observations. A dose-dependent increase in the disappearance of dopamine in alpha-MPT-pretreated rats was observed following icv administration of DT gamma E in the nucleus interstitialis striae terminalis, the paraventricular nucleus, the anterior hypothalamic nucleus and the zona incerta. In these same brain regions a decrease in the alpha-MPT-induced disappearance of dopamine was found following the administration of DT alpha E, but only after doses of 0.01, 0.1 and 1 microgram. In none of these regions were effects observed after 10 micrograms of DT alpha E. No effects were seen on dopamine utilization in the nucleus accumbens, caudate nucleus and median eminence after any of the doses of DT gamma E or DT alpha E. The alpha-MPT-induced disappearance of noradrenaline was significantly enhanced in the anterior hypothalamic nucleus of rats treated with DT gamma E. It is concluded that DT gamma E and DT alpha E induce opposite changes in the utilization of dopamine selectively in brain regions which are predominantly innervated by neurons belonging to the intradiencephalic dopamine systems.

Animals↗