Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraperitoneal administration of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and nonsulphated cholecystokinin octapeptide (CCK-8-NS) enhanced the latency of seizures induced by picrotoxin in mice. Experiments with N- and C-terminal fragments revealed that the C-terminal tetrapeptide (CCK-5-8) was the active centre of the CCK octapeptide molecule. The analogues CCK-8-SE and CCK-8-NS (dose range 0.2-6.4 mumol/kg) and caerulein dose range 0.1-0.8 mumol/kg) showed bell-shaped dose-effect curves, with the greatest maximum inhibition for CCK-8-NS. The peptide CCK-5-8 had weak anticonvulsant activity in comparison to the octapeptides, 3.2 mumol/kg and larger doses of the reference drug, diazepam, totally prevented picrotoxin-induced seizures and mortality. The maximum effect of the peptides tested was less than that of diazepam. Experiments with analogues and derivatives of CCK-5-8 demonstrated that the effectiveness of the beta-alanyl derivatives of CCK-5-8 were enhanced and that they were equipotent with CCK-8-SE. Of the CCK-2-8 analogues, Ser(SO3H)7-Ac-CCK-2-8-SE and Thr(SO3H)7-Ac-CCK-2-8-SE and Hyp(SO3H)-Ac-CCK-2-8-SE were slightly more active than CCK-8-SE.
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PMID:Structure-activity and dose-effect relationships of the antagonism of picrotoxin-induced seizures by cholecystokinin, fragments and analogues of cholecystokinin in mice. 631 93

The effects of several doses of intracerebroventricularly injected cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated scholecystokinin octapeptide (CCK-8-NS) were studied on electroconvulsive shock (ECS)-induced retrograde amnesia, as measured in a one-trial step-through passive avoidance paradigm. Both CCK-8-SE and CCK-8-NS were able to attenuate amnesia slightly when they were injected into rats 10 min prior to ECS treatment, possibly by reducing the severity of the ECS-induced seizures. Of the treatments carried out immediately after ECS, only the 0.8 pmole dose of CCK-8-NS could significantly restore retrograde amnesia. After treatment 20 min prior to testing 24-hr retention, no effect of the peptides was observed. The lack of a dose-dependency and of any effect on retrieval raises the possibility that the CCK octapeptides influence memory processes by an indirect mechanism.
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PMID:The effects of sulfated and nonsulfated cholecystokinin octapeptides on electroconvulsive shock-induced retrograde amnesia after intracerebroventricular administration in rats. 632 92

Recent studies have suggested that cholecystokinin may have a role in modulating the effects of the endogenous opioid system in physiological functions such as thermoregulation and pain control. However, the possible interaction of cholecystokinin and morphine in epileptogenesis is unknown. We studied the effect of subcutaneous morphine and intracerebroventricularly administered cholecystokinin octapeptide sulphate ester and receptor antagonists CCK-A (MK 329) and CCK-B (L 365,260) on seizures provoked by maximal electroshock in male Sprague-Dawley rats. Seizures were induced through electrode-gel-coated ear clip electrodes by a high voltage, high internal resistance constant current generator, 30 minutes after morphine administration and 10 minutes after cholecystokinin-8-SE, CCK-A and CCK-B infusion. Morphine decreased the length of the tonic component of the seizure and cholecystokinin potentiated this decrease. Cholecystokinin antagonists blocked the effects of both cholecystokinin and morphine. The results suggest that cholecystokinin acts as an endogenous agonist with opioids in the regulation of seizure susceptibility through both CCK-A and B receptors and may be responsible for part of the anticonvulsant action of morphine.
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PMID:Cholecystokinin potentiates morphine anticonvulsant action through both CCK-A and CCK-B receptors. 774 54

The release of cholecystokinin (CCK) in vitro has been shown to be influenced by NMDA receptors. In this study we have investigated whether excitotoxin-induced seizure activity affects the release and tissue content of CCK. Excitotoxin injection caused a significant decrease in CCK in ipsilateral frontal, parietal and temporal cortex by (30-54%) at 8 h compared to contralateral cortex and sham-operated controls and the effect was reversed by 24 h. No change was detected in occipital cortex, hippocampus and nucleus accumbens. The effect in frontal and temporal cortex was maximal at 8 h and could be completely prevented by treatment with MK-801(3 mg/kg i.p.). Anaesthesia (pentobarbital) alone or in combination with MK-801 did not affect peptide levels at 8 h. CCK mRNA levels were also studied quantitatively by slot-blot analysis but were unaffected at 6, 8 and 24 h after excitotoxin injection. The decrease in CCK tissue levels indicated that seizure activity stimulated CCK release which was confirmed in ex vivo experiments where K(+)-evoked (34 mM) CCK release was significantly enhanced in ipsilateral cerebral cortex at 6 h compared to contralateral cortex.
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PMID:Depletion of cortical cholecystokinin levels after excitotoxin injection into the nucleus basalis: sensitivity to MK-801. 777 62

Cholecystokinin (CCK) has emerged as an important mammalian neuropeptide, localized in peripheral organs and in the central nervous system. This review presents an overview of the molecular aspects of CCK peptides and CCK receptors, the anatomical distribution of CCK, the neurophysiological actions of CCK, release of CCK and effects of CCK on release of other neurotransmitters, and the actions of CCK on digestion, feeding, cardiovascular function, respiratory function, neurotoxicity and seizures, cancer cell proliferation, analgesia, sleep, sexual and reproductive behaviors, memory, anxiety, and dopamine-mediated exploratory and rewarded behaviors. Human clinical studies of CCK in feeding disorders and panic disorders are described. New findings are presented on potent, nonpeptide CCK antagonists, selective for the two CCK receptor subtypes, which demonstrate that endogenous CCK has biologically important effects on physiology and behavior.
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PMID:Biological actions of cholecystokinin. 793 54

The expression of neuropeptides and neurotrophic factors is altered in the hippocampus after seizure induction in rats. Because the increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNAs precede changes in neuropeptide expression after seizure, it is possible that BDNF and NGF mediate subsequent alterations in peptide expression. To test this hypothesis directly, BDNF or NGF was infused into the hippocampus and cortex of adult rats. To ascertain the regional specificity of any observed effects of neurotrophin administration on neuropeptide expression, infusions into the striatum were also studied. To control for specificity, vehicle was also infused into the same sites. Peptide and mRNA alterations were assessed by Northern analysis, immunohistochemistry and radioimmunoassay. BDNF produced elevations of peptide and mRNA for neuropeptide Y and cholecystokinin in hippocampus and cortex, and somatostatin in cortex. BDNF increased mRNAs for neuropeptide Y, cholecystokinin, substance P and dynorphin in striatum. In contrast, BDNF decreased dynorphin peptide and mRNA in hippocampus. NGF's effects were limited to small mRNA increases, without corresponding changes in peptide levels, for neuropeptide Y in hippocampus and striatum, substance P in cortex and cholecystokinin in striatum. The distinct and limited effects of NGF infusion on neuropeptide expression demonstrate that BDNF's effects are not non-specific results of protein infusion into the brain. These findings indicate that BDNF may play a regionally specific role in modulating neuropeptide expression in the normal brain as well as in various pathophysiological states.
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PMID:Regulation of neuropeptides in adult rat forebrain by the neurotrophins BDNF and NGF. 798 76

We measured lumbar cerebrospinal fluid (CSF) levels of somatostatin, cholecystokinin, neurotensin, atrial natriuretic factor, vasoactive inhibitory peptide, neuropeptide Y, adrenocorticotrophic hormone, corticotropin releasing hormone, beta-endorphin, metenkephalin, cortisol, alanine, glycine, aspartate, glutamate, taurine, and gamma-aminobutyric acid in 25 inpatients with epilepsy at known interictal and postictal times and in 11 neurologically normal volunteers. There were no significant differences between interictal or postictal complex partial seizures (CPS), postictal generalized tonic-clonic seizures (GTC), and control CSF neuropeptide, cortisol, and amino acid (AA) levels. However, there were nonsignificant trends for CSF levels of several neuropeptides to be increased after CPS and GTC as compared with interictal baseline levels. There were significant correlations between levels of certain CSF neuropeptides or (AAs) and serum antiepileptic drug (AED) levels. Several correlations were noted between CSF levels of AAs, including a correlation between the excitatory neurotransmitters aspartate and glutamate identified only after CPS.
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PMID:Cerebrospinal fluid levels of neuropeptides, cortisol, and amino acids in patients with epilepsy. 809 91

The inhibitory effects of ceruletide (CLT), a cholecystokinin-8 (CCK)-like peptide, were investigated in the epileptogenesis in the amygdaloid kindled rats. Lower doses of CLT (20-80 micrograms/kg) inhibited the progression of kindling process. After acquiring C5 stage, a higher dose (160 micrograms/kg) was required to suppress the seizure susceptibility. These results, in light of several previous studies showing no serious side effects, suggest that CLT might be useful as an anti-epileptogenic agent for clinical usage.
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PMID:Effect of ceruletide on epileptogenesis in amygdaloid kindled rats. 811 5

Immunocytochemistry and in situ hybridization techniques were used for investigating changes in cholecystokinin immunoreactivity and mRNA in the cerebral cortex and hippocampus after kainic acid-induced limbic seizures in the rat. Marked increases in cholecystokinin mRNA concentrations were observed in layers II/III and V/VI of the cerebral cortex, in CA1 pyramidal neurons of the hippocampus, and in presumptive basket cells of the dentate gyrus 1 and 2 days after the acute seizures. Whereas cholecystokinin mRNA contents returned to normal in the cerebral cortex and the CA1 sector at later intervals, high concentrations were observed in basket cells even 2 months after the initial seizures. Accordingly, cholecystokinin-like immunoreactivity was intensified in the cerebral cortex, CA1 sector and in presumed basket cells of the hippocampus 30 days after kainic acid. Besides its high content in basket cells, cholecystokinin-like immunoreactivity was primarily present in neuronal fibers or diffusely distributed in the respective brain area. In the hippocampus, strongly enhanced staining for cholecystokinin was also observed in the alveus, the stratum lacunosum moleculare, and in the inner molecular layer, suggesting increased concentrations of the peptide in afferent and efferent fibers of the hippocampus. The present experiments suggest a strong activation of cholecystokinin systems in the brain after kainic acid-induced limbic seizures in the rat. This is indicated by pronounced increases in cholecystokinin mRNA in the cortex and individual cell types of the hippocampus (basket cells, granule cells, and CA1 pyramidal neurons). The subsequent increases in cholecystokin immunoreactivity even surpass those in mRNA. The observed changes may be part of the self-defense mechanisms that protect the animals during subsequent epileptic episodes.
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PMID:Kainic acid seizures cause enhanced expression of cholecystokinin-octapeptide in the cortex and hippocampus of the rat. 827 98

Somatostatin-, neuropeptide Y-, neurokinin B- and cholecystokinin-containing neurons were investigated in the rat hippocampus in two chronic models of temporal lobe epilepsy, i.e. 30 days after rapid kindling or electrically induced status epilepticus (post-status epilepticus). After rapid kindling, somatostatin immunoreactivity was strongly increased in interneurons and in the outer and middle molecular layer of the dentate gyrus. In four of six post-status epilepticus rats (status epilepticus I rats), somatostatin immunoreactivity was slightly increased in the dorsal but decreased in the ventral dentate gyrus and molecular layer. Somatostatin immunoreactivity decreased in neurons of the dorsal hilus in the two other post-status epilepticus rats investigated, while a complete loss was found in the respective ventral extension (status epilepticus-II rats). These changes were associated with a different extent of neurodegeneration as assessed by Nissl staining. Similarly, neuropeptide Y immunoreactivity was enhanced in neurons of the hilus and in the middle and outer molecular layer of the dentate gyrus in the dorsal hippocampus of rapidly kindled and status epilepticus-I rats. Neuropeptide Y and neurokinin B immunoreactivity was enhanced in the mossy fibers of all post-status epilepticus rats, but not in the rapidly kindled rats. In status epilepticus-II rats, neuropeptide Y-and neurokinin B-positive fibers were also detected in the infrapyramidal region of the stratum oriens of CA3 and in the inner molecular layer of the dentate gyrus in the dorsal and ventral hippocampus respectively, labeling presumably sprouted mossy fibers. Increased staining of neuropeptide Y and neurokinin B was found in the alveus after rapid kindling. Cholecystokinin immunoreactivity was markedly increased in the cerebral cortex, Ammon's horn and the molecular layer of the dentate gyrus in the ventral hippocampus of rapidly kindled and post-status epilepticus rats. The lasting changes in the immunoreactive pattern of various peptides in the hippocampus may reflect functional modifications in the corresponding peptide-containing neurons. These changes may be involved in chronic epileptogenesis, which evolves in response to limbic seizures.
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PMID:Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy. 859 52


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