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Biomedical subjects

D De Wied

Publications and source records attributed to D De Wied.

At least 19 recordsLinked to original sources
PubMed1992

ACTH: a structure-activity study on pilocarpine-induced epilepsy.

Intracerebroventricularly applied pilocarpine (2.4 mg/2 microliters) immediately produced symptoms of epilepsy, ranging from akinesia to motor seizures, in rats. Whereas ACTH-(1-39), ACTH-(1-24), ACTH-(1-18), ACTH-(1-16) and ACTH-(18-39) were not active, subcutaneous pretreatment with smaller ACTH-like fragments, such as ACTH-(4-9), ACTH-(4-10), ACTH-(4-10)(7D-Phe), ACTH-(7-16), and Org2766, reduced the severity of the epilepsy. Moreover, fewer rats developed motor seizures. Thus, ACTH fragments devoid of peripheral endocrine activity reduce pilocarpine-induced epileptiform activity in rats. A narrow bell-shaped dose-response relationship was found. Except for ACTH-(7-16), which was active in a dose of 1 and 10 micrograms/rat s.c., the other fragments were only active at one dose (10 micrograms/rat). The anti-epileptic properties appeared to reside in the sequence 1-16, and more specifically in the sequences 4-7 and 7-16, of the ACTH molecule.

Adrenocorticotropic Hormone↗
PubMed1992

Antipyretic effect of central arginine8-vasopressin treatment: V1 receptors specifically involved?

Intracerebroventricular (i.c.v.) administration of the neurohypophyseal neuropeptide arginine8-vasopressin (AVP) results in a dose-dependent attenuation of endotoxin-induced fever (EIF) in rats. Specific antagonists of the neuropeptided(CH2)5[Tyr(Me)2]AVP for V1 receptors, d(CH2)5[dlle2lle4]AVP for the V2 receptors and Des-Gly,NH2d(CH2)5[Tyr)Me2)Thr4Orn8]vasotocin, an antagonist of the oxytocin receptors (AOXT), failed to modify EIF when administered i.c.v. Relatively high doses (100 ng) of all three peptide antagonists effectively blocked the antipyretic effect of AVP. Administered in smaller doses (10 or 30 ng), however, a more specific interaction was observed, i.e. the V1 antagonist being the only effective compound in preventing the effect of AVP. Although the data indicate that peptide-antagonist interactions should be interpreted carefully, the present experiments confirm previous observations on the involvement of V1-type receptors in the antipyretic action of AVP and suggest additional interactions with V2 vasopressinergic and oxytocinergic receptors.

Animals↗
PubMed1991

Ontogenetic and seasonal changes in immunoreactive vasotocin in the canary brain.

Using immunocytochemistry the central VT system of the canary was examined during ontogeny and throughout the season. At 4 weeks of age no VT-immunoreactive staining in the bed nucleus of the stria terminalis and lateral septum was present, but VT-containing cells and fibers were clearly visible in the nucleus paraventricularis of the hypothalamus. At 13 weeks of age a weak VT immunoreactivity appeared in the bed nucleus of the stria terminalis and lateral septum. This VT immunostaining increased progressively till at the age of 28 weeks adult levels were reached. In adulthood, cells and fibers in the lateral septum and the bed nucleus of the stria terminalis contained the highest amounts of immunoreactive VT during the breeding season, whereas during the molt, in august, a decreased VT immunostaining was noted. These seasonal changes in VT immunostaining coincided with variations in circulating testosterone level, which is high during the breeding season and low during the molt. In the ventral capsular region surrounding the nucleus robustus archistriatalis a clear VT-immunoreactive fiber pattern was demonstrated at the age of 8 and 13 weeks in both female and male canaries. Although the size of this nucleus varies during the season no seasonal changes in the VT-immunoreactive pattern surrounding the RA were detected. The data suggest that the activity of the VT system slowly increases during development. At adulthood seasonal and gonadal hormone-dependent changes occur in the limbic VT system only. The VT immunostaining associated with the nucleus robustus archistriatalis however, is resistant to seasonal and gonadal influences.

Aging↗
PubMed1991

Effect of a vasotocin analog on singing behavior in the canary.

Groups of juvenile and 1-year-old male canaries were treated briefly with the vasotocin (VT) analog desGly(NH2)9d(CH2)5-[Tyr(Me)2,Thr4, Orn8]VT (dGVTA) during four time intervals between September and February. The canaries received subcutaneously testosterone-containing silastic implants at the start of the VT analog treatment to assure that despite age and season differences the birds would all have comparable plasma levels of testosterone. The VT analog was administered subcutaneously (0.7 micrograms/100 microliters) during the first 3 days (3 injections daily) of chronic testosterone treatment. Observations on the singing behavior were carried out between Day 8 and Day 30 after implantation of the testosterone-filled silastic tubing. The short-term administration of the VT analog influenced the amount of singing behavior during a 30-min observation interval measured 1 to 4 weeks later. Despite age differences the effect of dGVTA held and seemed more related to season than to age. The song duration (seconds of song/30 min) was affected in a dual mode. In early autumn the VT analog enhanced song duration of testosterone-primed canaries, but the same VT analog decreased song duration in the period November/January. These results suggest that the neuropeptide VT is implicated in control of seasonal changes in singing behavior.

Age Factors↗
PubMed1991

Shock-prod burying test in rats: autonomic and behavioral responses.

Heart rate (HR), core temperature (CT) and gross locomotor activity (GLA) were recorded in rats by a computerized telemetry system before, during and after 15-min exposure to a constantly electrified (2mA) or nonelectrified (0mA) prod which was presented through a hole in the home cage with woodshavings on the floor [shock-prod burying (SPB) test]. Measurement of both autonomic and behavioral response continued up to 60 min after introduction of the prod in the home cage. Twenty-four h after the SPB test, rats were tested for retention. During the SPB test, significant increases in HR, respective to baseline values, were observed in both the 2mA and 0mA group, but the tachycardiac response in the former group significantly outweighed that in the latter group. In shocked rats, HR remained elevated during the entire 45-min posttest period, whereas HR declined immediately after removal of the prod in nonshocked animals. An onset in rise in CT was observed in the 2mA, but not in the 0mA group, during prod exposure time, which eventually resulted in an additional-more than two-fold--increase after termination of the test and outlasted total recording time. Marked behavioral activation was observed in the 2mA group, whereas the 0mA responded to a lesser extent. Approach and exploration of the prod was reduced when the prod was electrified. The total time spent by rats burying the prod was significantly longer in the shocked than in the nonshocked group. When exposed to the nonelectrified prod after 24 h, total burying time was reduced in the 2mA group but still significantly longer than in the 0mA group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Central vasopressin impairs the baroreceptor heart rate reflex in conscious rats.

In conscious, unrestrained rats, the resting values of mean arterial blood pressure (BP) and heart rate (HR) as well as the baroreceptor heart rate reflex (BHR) were measured before and after intracerebroventricular (i.c.v.) application of arginine vasopressin (AVP). The BHR was induced by intravenous (i.v.) injection of different doses of phenylephrine. Basal values of BP and HR were 114 +/- 2.4 mm Hg and 376 +/- 13 beats/min (mean +/- SE). These values were not altered by i.c.v. application of vehicle or 5, 10, 30, 300, 3,000 pg AVP or 1 pg AVP antagonist [(D(CH2)5Tyr(Me)-AVP)]. Ten and 30 pg AVP administered i.c.v. attenuated the phenylephrine-induced decrease in HR. Lower or higher doses of AVP were not effective. Administration of the AVP antagonist i.c.v. sensitized the BHR. When the BHR was rechecked 24 h after treatment, the influence of the i.c.v.-administered peptides had disappeared. We conclude that AVP through the cerebrospinal fluid impairs the baroreflex regulation.

Animals↗
PubMed1990

Effects of pituitary beta-endorphin secretagogues on the concentration of beta-endorphin in rat cerebrospinal fluid: evidence for a role of vasopressin in the regulation of brain beta-endorphin release.

The concentration of beta-endorphin-immunoreactivity (beta E-IR) in cerebrospinal fluid (CSF) and plasma of rats was determined following intracerebroventricular (ICV) treatment of conscious animals with substances known to stimulate the release of beta E and other pro-opiomelanocortin (POMC)-derived peptides at the level of the anterior and intermediate lobes of the pituitary. The beta-adrenoceptor agoinst isoproterenol (ISO) did not influence the concentration of beta E-IR in CSF collected 5-60 min after ICV administration of doses ranging from 3 to 30,000 pg/rat. Plasma beta E-IR levels, however, were significantly increased 20 min following ICV injection of 30,000 pg ISO. ICV treatment of animals with ovine corticotropin-releasing factor (CRF; 30-30,000 pg/rat) also did not affect CSF levels of beta E-IR, whereas CRF in a dose of 30 pg significantly decreased, and in doses of 300-30,000 pg enhanced plasma beta E-IR concentrations as determined by 20 min following treatments. ICV injection of arginine8-vasopressin (AVP) in doses of 10-1,000 pg/rat dose-dependently elevated the beta E-IR concentration in CSF without affecting plasma beta E-IR levels. This AVP-induced increase in CSF beta E-IR was maximal 20-35 min and beta E-IR levels had returned to basal 60 min following treatment. The data indicate that AVP and not ISO and CRF is a stimulator of CSF levels of beta E-IR. As beta E-IR in CSF likely originates from brain POMC neurons, these results suggest the hot vasopressin may be a physiological regulator of brain POMC activity, and may act as a releasing factor for POMC-derived peptides in the brain.

Animals↗
PubMed1989

N alpha-acetyl-[Arg8]vasopressin antagonizes the behavioral effect of [Cyt6]vasopressin-(5-9), but not of vasopressin.

It has been found recently that N alpha-acetyl-[Arg8]vasopressin (Ac-VP) is present in the brain of rats. The physiological significance of this peptide is as yet unknown. Therefore, the central nervous system effects of this peptide were investigated, namely, its effects on passive avoidance behavior, exploratory behavior and body temperature. The interaction of Ac-VP with the central nervous system effects of vasopressin (VP) was also studied. Ac-VP had a slight agonistic effect on passive avoidance behavior, i.e. it facilitated passive avoidance behavior at a dose 100 times higher than that of VP. Relatively low doses (3-10 ng) of Ac-VP attenuated passive avoidance behavior, which suggests that Ac-VP interfered with an endogenous compound involved in the control of passive avoidance responding. Ac-VP was also able, albeit in higher doses (30 ng), to competitively antagonize the effect of [Cyt6]VP-(5-9), a highly potent, putative endogenous metabolite of vasopressin in the rat brain. This antagonism could be due to an interaction of Ac-VP with sites other than the V1 vasopressin receptor. Ac-VP had no significant influence on other central nervous system effects of the hormonally active nonapeptide VP, such as exploratory behavior and body temperature. These effects were readily antagonized by the V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)VP. Ac-VP may be competitive antagonist of behaviorally active vasopressin metabolite(s) in the brain.

Animals↗
PubMed1989

Effects of ACTH-(11-24) on the corticosteroid production of isolated adrenocortical cells.

The steroidogenic action of ACTH-(11-24) was studied on isolated zona glomerulosa and zona fasciculata cells dispersed by collagenase. ACTH-(11-24) stimulated the corticosterone production of zona fasciculata cells and the aldosterone production of zona glomerulosa cells; in addition, it potentiated the effects of ACTH-(1-39) on both cell systems. It is suggested that the ACTH molecule contains more active sites for steroidogenesis than usually acknowledged, as has been found for lipolysis and behavior.

Adrenal Cortex↗
PubMed1989

Vasopressin, vasopressin fragments and a C-terminal peptide of the vasopressin precursor share cardiovascular effects when microinjected into the nucleus tractus solitarii.

Arginine-vasopressin (VP), the VP fragments VP-(1-8), [pGlu4,Cyt6]VP-(4-9) and -(4-8), and a fragment of the C-terminal glycopeptide of the VP precursor [CPP-(22-39)] decreased blood pressure and heart rate in anesthetized rats when microinjected bilaterally into the nucleus tractus solitarii (NTS). The magnitude of the effect was similar at doses of 20 pg, except for VP-(1-8) which required about 500 pg. The strongest decrease in blood pressure and heart rate was observed with 100 pg VP. Higher doses of other peptides either were ineffective [CPP-(22-39)] or increased blood pressure [( pGlu4,Cyt6]VP-(4-9) and -(4-8)). VP metabolites thus may participate in the control of cardiovascular functions exerted by VP. The effect of CPP-(22-39) indicates that the C-terminal glycopeptide of the VP precursor contains biological activity, which may support the cardiovascular action of VP in the NTS.

Animals↗
PubMed1988

Leu-Phe cleaving endopeptidase activity, gamma-endorphin, and beta-endorphin in the rat pituitary gland and brain. Effect of adrenalectomy and corticosterone substitution.

The influence of adrenalectomy and corticosterone substitution was investigated on Leu-Phe cleaving endopeptidase activity and on the levels of gamma-endorphin and beta-endorphin in the pituitary gland and the brain. The enzyme activity was quantitated by a specific radiometric assay based on the cleavage of the Leu17-Phe18 bond in a NH2- and COOH-terminally protected synthetic substrate which was analogous to beta-endorphin-(15-19). This activity may mimick the formation of gamma-endorphin. beta-Endorphin and gamma-endorphin were measured by specific radioimmunoassays. After 14 days of adrenalectomy enzyme activity had increased in anterior (15%) and neurointermediate lobes of the pituitary gland (30%), hypothalamus (25%), and liver (15%). This increase was prevented when the adrenalectomized animals were subjected to chronic corticosterone substitution by subcutaneous implantation of a pellet of 100 mg. Extirpation of only the adrenal medulla did not affect the Leu-Phe cleaving activity. Enzyme activity in the septum, hippocampus, and cerebellum had not changed after adrenalectomy. Determination of immunoreactive levels of gamma- and beta-endorphins showed that in the anterior pituitary gland gamma- and beta-endorphins had increased by 275 and 300%, respectively, 14 days after adrenalectomy. No significant changes were observed in endorphin levels of the intermediate lobe of the pituitary gland, hypothalamus, hippocampus, and septum. The results indicate that Leu-Phe cleaving endopeptidase activity in sensitive to glucocorticoids in tissues containing proopiomelanocortin-producing cells, i.e., anterior and neurointermediate pituitary gland and the hypothalamus. In the anterior pituitary gland it is correlated with the levels of gamma- and beta-endorphins.

Adrenalectomy↗
PubMed1986

Endorphinergic mechanisms in cerebral blood flow autoregulation.

The influence of naturally occurring opioid peptides (Met-enkephalin (Met-Enk), dynorphin (DYN), beta-endorphin (beta-EP)) as well as morphine and the opiate antagonist naloxone and specific antisera on cerebral blood flow autoregulation was studied in anesthetized, artificially ventilated rats. Local hypothalamic blood flow (CBF, H2-gas clearance technique) and total cerebral blood volume (CBV, photoelectric method) were simultaneously recorded. Autoregulation was tested by determining CBF and CBV during consecutive stepwise lowering of the systemic mean arterial pressure to 80, 60 and 40 mm Hg, by hemorrhage. Resting CBF decreased following Met-Enk, DYN, beta-EP or morphine administration without simultaneous changes in CBV. Naloxone administration, on the contrary, increased CBV without affecting local CBF. Autoregulation of cerebral blood flow was maintained until 80 mm Hg, but not completely at 60 and 40 mm Hg arterial pressure in the control group. General opiate receptor blockade by 1 mg/kg s.c. naloxone abolished autoregulation at all levels, since CBF and CBV passively followed the arterial pressure changes. Intracerebroventricularly injected naloxone (1 microgram/kg) as well as a specific antiserum against beta-EP, but not against Met-Enk or DYN, resulted in the very same effect as peripherally injected naloxone. The present findings suggest that central, periventricular beta-endorphinergic mechanisms might play a major role in CBF autoregulation.

Animals↗
PubMed1985

Gamma-type endorphins: neurolepticum-like and antipsychotic action.

The hypothesis implicating the gamma-type endorphins in schizophrenia was initially based on animal data showing commonalities between the behavioral effects of these peptides and neuroleptics. Clinical studies have shown that these peptides have an antipsychotic action in a number of patients suffering from schizophrenic psychosis. The patients responding to the peptides are characterized by features at least partly resembling those characterizing type I schizophrenia. This may be consistent with the animal data showing that gamma-type endorphins may directly or indirectly control certain dopaminergic systems present in the nucleus accumbens. Genetical differences may exist between patients susceptible to and not susceptible to gamma-type endorphins, as has been concluded from studies concerning antigens of the HLA system.

Antipsychotic Agents↗