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Biomedical subjects

G Telegdy

Publications and source records attributed to G Telegdy.

At least 37 records · Page 2Linked to original sources
PubMed2000

The effects of valproate on the arachidonic acid metabolism of rat brain microvessels and of platelets.

Long-term administration of the antiepileptic drug valproate can induce hematologic, hepatic and endocrine abnormalities and morphologic alterations in the brain capillaries and glial cells. Valproate elicits bone marrow suppression, reducing the number of red blood cells and platelets, and causes platelet functional abnormalities. Various data suggest that more than one mechanism of valproate-associated toxicity may exist, but the pathomechanism of cell function alterations elicited by valproate has not yet been elucidated. The reported ex vivo experiments were designed to investigate the effects of valproate on the arachidonic acid cascade of rat brain capillaries and platelets. Valproate was administered (300 mg/kg body weight/day) in the drinking water to male Wistar rats for 2 weeks. Isolated platelets and brain microvessels were labelled with [14C]arachidonic acid and the released [14C]eicosanoids were separated by overpressure thin-layer chromatography and determined quantitatively by liquid scintillation counting. Valproate treatment reduced the synthesis of cyclooxygenase and lipoxygenase products in rat platelets. In brain microvessels valproate stimulated the synthesis of lipoxygenase metabolites and attenuated the cyclooxygenase pathway. Modifications of the arachidonate cascade in platelets and brain microvessels may contribute to the cell function alterations caused by valproate.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2000

Effects of brain natriuretic peptide on pituitary-adrenal activation in rats.

The aim of this study was to characterize the effects of brain natriuretic peptide (BNP) on the hypothalamo-pituitary-adrenal (HPA) responses to different stress paradigms (ether stress, electric shock and restraint). Rats were subjected to the stressful stimuli after intracerebroventricular administration of BNP (32.5 ng-6.5 microg) and plasma corticosterone was used as an indicator of the HPA activation. BNP did not modify the basal secretion, but inhibited the stress-induced rise in plasma corticosterone in a dose-dependent manner. BNP proved most effective in decreasing the corticosterone response to ether stress and attenuated the electric shock and restraint-induced HPA activation to a lesser extent. These results confirm the view that BNP takes part in the regulation of the HPA system.

Animals↗
PubMed2000

Isatin (Indole-2, 3-dione) inhibits natriuretic peptide-induced hyperthermia in rats.

The effects of an endogenous indole, isatin (indole-2, 3-dione), on the hyperthermia induced by atrial natriuretic peptide (ANP-28), brain natriuretic peptide (BNP-32), and C-type natriuretic peptide (CNP-22) were investigated in rats. Intracerebroventricular administration of each peptide in a dose of 1 microg caused elevations in colon temperature 30 and 60 min after injection. An intraperitoneal (i.p.) injection of isatin (50 mg/kg) abolished the natriuretic peptide-induced hyperthermia. These data reinforce the possible involvement of natriuretic peptides in thermoregulatory processes in the central nervous system, and suggest that isatin might counteract their hyperthermic effect in vivo.

Analysis of Variance↗
PubMed2000

The action of isatin (2,3-dioxoindole) an endogenous indole on brain natriuretic and C-type natriuretic peptide-induced facilitation of memory consolidation in passive-avoidance learning in rats.

Isatin is an endogenous indole which has been shown to counteract some of the effects of atrial natriuretic peptide (ANP) both in vitro and in vivo. The present study was designed to determine whether it could antagonise in vivo effects of the related peptides brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). The model used was consolidation of memory in a one-trial step-through passive-avoidance paradigm in the rat. Previous studies have shown that all three peptides (1 microg intracerebroventricular) can consolidate such learning and increase latency to entry a dark box. Isatin was given intraperitoneally at doses of 5, 10 and 50 mg/kg before the peptide, or a saline control. Both BNP and CNP significantly increased the latency of entry. Isatin alone had no effect. Isatin reduced the effect of both BNP and CNP; this was significant for its effect on BNP at 50 mg/kg and on CNP at both 10 and 50 mg/kg. These results show that isatin can inhibit behavioural effects of BNP and CNP as well as ANP.

Animals↗
PubMed2000

Effects of orexins on the hypothalamic-pituitary-adrenal system.

The effects of the recently identified neuropeptides orexin-A and orexin-B on the hypothalamic-pituitary-adrenal (HPA) system were investigated. An in vivo system was used to assess the central effects of both orexin-A and orexin-B. Different doses of the orexins (2.8-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and plasma corticosterone was used as an index of the degree of the activation of the HPA system. Both peptides exhibited a clear dose-response action, although orexin-B proved to be less effective than orexin-A. Pretreatment with the corticotropin-releasing hormone (CRH) antagonist alpha-helical CRH9-41 completely prevented the action of the orexins. Orexin-A, orexin-B or adrenocorticotropic hormone (ACTH) was further administered intraperitoneally (i.p.). While ACTH evoked a significant adrenal response, the orexins did not influence the basal secretion. Adrenal slices, oxygenized and perifused with Krebs' solution, were also treated with orexin-A, orexin-B or ACTH. Both orexins failed to modify the release of corticosterone, but ACTH induced a marked adrenal response. This study suggests that these appetite-regulating peptides might activate the HPA system at a central level but neither orexin-A nor orexin-B appears to modulate directly the adrenal corticosterone release.

Adrenal Glands↗
PubMed2000

Platelet arachidonate cascade of migraineurs in the interictal phase.

Morphological and functional alterations of platelets in migraineurs may be linked to the development of migraine. We examined the eicosanoid synthesis of platelets of untreated female migraineurs in a headache-free period and compared it to that of age- and blood group-matched healthy female volunteers. In the platelets of headache-free migraineurs significantly less amounts of anti-aggregatory prostaglandin D2 and prostacyclin, as well as of 12-L-hydroxy-5,8,10-heptadecatrienoic acid (a potent endogenous inducer of endothelial prostacyclin production) were produced, while the synthesis of platelet aggregatory thromboxane did not differ when compared to that of healthy women. These results suggest that the platelet eicosanoids of migraineurs in the headache-free period might promote the development of cellular, vascular and neurological events inducing headache.

Adult↗
PubMed2000

Involvement of endogenous corticotropin-releasing factor in mediation of neuroendocrine and behavioral effects to alpha-melanocyte-stimulating hormone.

The present work was to study if the alpha-melanocyte-stimulating hormone (alpha-MSH) was involved in activation of the pituitary-adrenal axis (PAA) in rats. The hormone increased plasma corticosterone (CORT) level, and induced an anxiogenic response as indicated by results from the elevated plus-maze test. Intracerebroventricular administration of corticotropin-releasing factor (CRF) antiserum (1:10, 1:20 and 1:100 dilutions in 1microl volume), overcame both the anxiogenic response and the PAA activating effect induced by alpha-MSH (50 microg s.c.) in a concentration-dependent manner. CRF antibody at the doses applied did not modify either the elevated plus-maze responses or CORT level by itself. Our results reveal that both the anxiogenic and the PAA activating effects of alpha-MSH are mediated by CRF.

Adrenal Glands↗
PubMed1999

Vasoactive substances produced by cultured rat brain endothelial cells.

The vasoactive substances synthesized by primary cultures of rat brain endothelial cells were investigated and compared to those from two, immortalized cell lines, RBE4 and GP8. The vasoactivity of endothelium-derived substances was measured on isolated canine coronary artery. Vascular tone was significantly decreased by both primary and GP8, but not by RBE4 cells. Indomethacin pretreatment of primary and GP8 cells turned vasorelaxation into contraction while N(omega)-nitro-L-arginine pretreatment decreased the vasorelaxation induced by primary, but not by GP8 cells. Eicosanoid production was determined after incubation with [14C]arachidonic acid. The predominant vasoactive eicosanoid was prostaglandin E2 in both primary and GP8 cells. RBE4 cells synthetized mainly prostaglandin E2 and thromboxane B2 and significantly less prostaglandin E2 than did either primary or GP8 cells. The capacity of cerebral endothelium to regulate vascular tone by production of dilator and constrictor substances can be preserved under certain circumstances in immortalized cell lines.

Animals↗
PubMed1999

Neurotransmitter-mediated open-field behavioral action of CGRP.

The effects of central administration of calcitonin gene-related peptide (CGRP) on open-field activity were examined in male rats. Three doses (250 ng, 500 ng and 1 microg) of CGRP given intracerebroventricularly (i.c.v.) were tested on the ambulatory, rearing and grooming activities of the animals. One microg of peptide significantly decreased the ambulatory activity and increased the rearing and grooming activities 30 min after the treatment. The animals were pretreated with different receptor antagonists in doses which by itself did not affect the behavioural paradigm. The decrease in ambulation induced by CGRP was antagonized by acetylcholine-, opioid-, 5HT-receptor and beta-adrenoceptor antagonists. CGRP induced increase in rearing activity was blocked by naloxone, phenoxybenzamine and propranolol. The CGRP-induced increase in grooming behavior was prevented by atropine, haloperidol, naloxone, methysergide and propranolol. The results suggest that different neurotransmitter systems are involved in the action of CGRP on open-field behavior in rats.

Animals↗
PubMed1999

Effects of pituitary adenylate cyclase-activating polypeptide on the cyclooxygenase pathway of rat platelets and on platelet aggregation.

Several data suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of local circulation. One possible role of PACAP in the regulation of circulation is that, it may modify the cyclooxygenase pathway of the arachidonate cascade in platelets. Our study was designed to study the effect of PACAP on the cyclooxygenase pathway of rat platelets and on platelet aggregation. PACAP (10(-7) and 10(-6) M) significantly inhibited the cyclooxygenase pathway of platelets, mostly the thromboxane synthesis. Pretreatment with a PACAP receptor antagonist, PACAP(6-38), or with an inhibitor of protein kinase A, H-89, shows that the effects of PACAP on the cyclooxygenase pathway were diminished. In the aggregation studies, PACAP inhibited both the arachidonic acid-induced and the thrombin-induced platelet aggregation. It can be concluded that PACAP inhibits the cyclooxygenase pathway of rat platelets via a specific PACAP receptor-activated, cAMP-dependent pathway, and these effects of PACAP are involved in the inhibition of platelet aggregation.

Animals↗
PubMed1999

Hyperthermic effect of centrally administered natriuretic peptides in the rat.

The effects of atrial natriuretic peptide (ANP-28), brain natriuretic peptide (BNP-32) and C-type natriuretic peptide (CNP-22) on body temperature were investigated in rats. Intracerebroventricular administration of each peptide in doses of 400 or 1000 ng caused a dose-related elevation in colon temperature 30 and 60 min after injection. A 40 ng dose of ANP-28 was also hyperthermic at 60 min. An intramuscular (i.m.) injection of noraminophenazone (a cyclooxygenase inhibitor) abolished the natriuretic peptide-induced hyperthermia. The results show that natriuretic peptides may participate in thermoregulatory processes in the central nervous system, and that their hyperthermic effect may be mediated via a cyclooxygenase-involved pathway.

Animals↗
PubMed1999

Pituitary adenylate cyclase-activating polypeptide inhibits the cyclooxygenase pathway of rat cerebral microvessels.

The presence of nerve endings containing pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) around cerebral microvessels suggests that these peptides have regulatory roles in the cerebral microcirculation. Prostanoids synthesized by the cerebrovascular endothelium have a determining role in the regulation of the brain circulation. In the present study, the effects of PACAP and VIP on the cyclooxygenase pathway of cerebral microvessels were investigated. The isolated microvessels were incubated with 1-14C-arachidonic acid and different concentrations of the peptides. The prostanoids formed were separated by means of overpressure thin-layer chromatography, and were quantitatively determined by liquid scintillation. Higher concentrations (10-7 and 10-6 mol L-1) of PACAP significantly inhibited the activity of the cyclooxygenase pathway, whereas VIP had no significant effect on it. As regards the cyclooxygenase metabolites, the syntheses of thromboxane A2 and prostaglandin D2 were inhibited significantly. PACAP and VIP are known to increase the intracellular cAMP level in the cerebral microvessels and in the present experiments the protein kinase A inhibitor H-89 attenuated the effect of PACAP on prostanoid synthesis. It is concluded that the cyclooxygenase pathway of rat cerebral microvessels is more sensitive to PACAP than to VIP. The inhibitory effect of PACAP on prostanoid synthesis is mediated via a cAMP-dependent pathway. By inhibiting the formation of vasoactive prostanoids, PACAP can decrease the vasoreactivity of the microvessels.

Adenylyl Cyclases↗
PubMed1999

Action of C-type natriuretic peptide (CNP) on passive avoidance learning in rats: involvement of transmitters.

The action of C-type of natriuretic peptide (CNP) was tested on one-way passive avoidance learning in rats. The involvement of transmitters was investigated by pretreating the animals with different receptor blockers. CNP administered into the lateral brain ventricle caused a dose-dependent facilitation of learning and consolidation of passive avoidance learning, but was ineffective on retrieval. Pretreatment of the animals with atropine, haloperidol or the nitric oxide synthase inhibitor nitro-L-arginine abolished the action of CNP. Phenoxybenzamine, naloxone, bicuculline, propranolol and methysergide were ineffective in modifying the action of CNP on consolidation. The results suggest that CNP is able to improve the learning and consolidation of learning in a passive avoidance paradigm, but is ineffective on retrieval processes. In the action of CNP, dopamine, acetylcholine and nitric oxide could be the mediating transmitters.

Animals↗
PubMed1999

Valproate treatment and platelet function: the role of arachidonate metabolites.

PURPOSE: Valproate (VPA) is an extensively used drug in the therapy of epilepsies. One of the most frequently reported side effects of VPA is hemorrhagic diathesis. Some authors emphasized the decreased platelet count as the basis of VPA-induced hemorrhagic diathesis, but some reports suggested that a significant proportion of patients with normal platelet count may still have an altered platelet function. The mechanism of the VPA-induced platelet dysfunction has not yet been elucidated. A determining element of platelet functions is the arachidonate cascade. Present ex vivo experiments were designed to determine whether a relation exists between the incidence of hemostasis caused by VPA and the effect of this drug on the arachidonate cascade of platelets. METHODS: Platelets were isolated from patients receiving long-term VPA treatment (serum level, 36.04+/-16.12 microg/ml; n = 10) or carbamazepine (CBZ) treatment (serum level, 5.24+/-2.67 microg/ml; n = 10) and were labeled with [14C]arachidonic acid. (CBZ-treated patients were chosen as a control group, because CBZ causes blood dyscrasias similar to those elicited by VPA, but there has been no report that CBZ induces a platelet dysfunction.) The 14C-eicosanoids were separated by means of overpressure thin-layer chromatography and determined quantitatively by liquid scintillation. RESULTS: Even when the mean plasma concentration of the drug was low, VPA treatment reduced the activity of the arachidonate cascade in platelets. VPA effectively inhibited the cyclooxygenase pathway and the synthesis of the strong platelet aggregator thromboxane A2. CONCLUSIONS: Inhibition of the platelet arachidonate cascade may contribute to the platelet-function alterations caused by VPA.

Adult↗
PubMed1998

Further evidence that nitric oxide modifies acute and chronic morphine actions in mice.

The effects of the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine (L-NNA, 2.5-10 microg i.c.v.), and the NO synthesis precursor, L-arginine (L-Arg, 2.5-10 microg i.c.v.), on morphine-induced analgesia, and on morphine-induced tolerance and dependence were examined in mice. Administration of L-NNA diminished the morphine-induced analgesia. L-Arg pretreatment increased the analgesic effect of morphine. Repeated pretreatment (three times, at 24-h intervals) with L-NNA diminished both acute and chronic tolerance to morphine, whereas both the acute and the chronic morphine-induced tolerance increased after the repeated (three times, at 24-h intervals) administration of L-Arg. Neither L-NNA nor L-Arg affected the signs of morphine dependence, as assessed by naloxone (1 mg/kg, s.c.)-precipitated withdrawal. Our data suggest that increased NO synthesis potentiates morphine analgesia and enhances the development of morphine tolerance in mice.

Analgesia↗
PubMed1998

Effects of C-type natriuretic peptide on pituitary-adrenal activation in rats.

The effects of C-type natriuretic peptide (CNP) on the hypothalamo-pituitary-adrenal system response to different stressors was studied. Various doses of CNP (0.2, 2, 4 microg) were injected into the lateral cerebral ventricle of freely moving rats 30 min before stress and activation of the adrenal was measured by plasma corticosterone. CNP did not affect basal corticosterone secretion in the doses applied, but inhibited in a dose-dependent manner the increase in plasma corticosterone induced by ether stress, electric shock and restraint. CNP exerted a more profound inhibitory effect on the response to ether stress than on that to electric shock or restraint. These results suggest that CNP acts centrally and to a different extent on the responses to different stresses.

Animals↗