Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistological and in situ hybridization techniques were used to study the influence of kainic acid-induced seizures and of pentylenetetrazol kindling on neurokinin B immunoreactivity and neurokinin B mRNA in the rat hippocampus. Pronounced increases in neurokinin B immunoreactivity were observed in the terminal field of mossy fibres 10-60 days after intraperitoneal injection of kainic acid. These slow but persistent increases in immunoreactivity were accompanied by markedly enhanced expression of neurokinin B mRNA in the granule cells and in hilar interneurons adjacent to the granule cell layer. These changes were preceded by transient increases in neurokinin B mRNA and immunoreactivity in CA1 pyramidal cell layer two and 10 days after kainic acid, which, however, subsided later on. Pentylenetetrazol kindling caused similar increases in neurokinin B mRNA expression in granule cells and in CA1 pyramidal cells, but not in hilar interneurons. In CA1, increased neurokinin B message was present two days after termination of the kindling procedure but not after 10 days. Sixty days after kainic acid injection, neurokinin B immunoreactivity extended to the inner-third of the molecular layer of the dentate gyrus. After pentylenetetrazol kindling, a neurokinin B-immunoreactive band was observed in the infrapyramidal region of CA3. Lesions of the dentate granule cells by local injection of colchicine in kainic acid-treated rats abolished the supragranular neurokinin B-positive staining, whereas it was almost unchanged after transection of the ventral hippocampal commissure. These observations suggest that neurokinin B immunoreactivity may be located in ipsilateral mossy fibres undergoing collateral sprouting to the inner molecular layer or to the infrapyramidal region in CA3, respectively. Preprotachykinin A mRNA, which encodes for neurokinin A and substance P, and substance P immunoreactivity were not changed in the hippocampus of epileptic rats compared with untreated animals. The observed changes in neurokinin B immunoreactivity and mRNA indicate that specific functional and morphological changes may be induced in hippocampal neurons by recurrent limbic seizures.
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PMID:Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat. 127 53

We studied the effects of modification of duration of seizures induced by electroconvulsive stimuli (ECS) on the changes in concentration of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP) and neurotensin (NT)-like immunoreactivity (-LI) in specific rat brain regions. Rats were divided into groups pretreated with saline, indomethacin, flurbiprofen or diazepam prior to either six sham ECSs or six ECSs. After sacrifice by focused microwave irradiation, brains were dissected into frontal cortex, occipital cortex, striatum, hippocampus, pituitary and hypothalamic sections. Peptides were extracted and measured in extract aliquots by specific radioimmunoassays. Repeated ECS increased NPY-LI and NKA-LI in the hippocampus and the occipital cortex. No effect on SP-LI or NT-LI was found. Indomethacin and flurbiprofen had no effect on the tonic seizure time following ECS, and they did not affect the ECS-induced alterations of the brain peptides. Diazepam pretreatment decreased the tonic seizure time following ECS in a dose-dependent manner. However, diazepam did not modify the ECS-induced increase in NPY-LI and NKA-LI concentrations. The results firmly establish that ECS leads to specific peptide increases in discrete rat brain regions and raise the possibility that such changes may not entirely be a consequence of seizures per se.
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PMID:Electroconvulsive stimuli and brain peptides: effect of modification of seizure duration on neuropeptide Y, neurokinin A, substance P and neurotensin. 128 45

Patients with medically intractable temporal lobe epilepsy (TLE) undergo medial temporal lobectomy with hippocampectomy for one of two reasons. (1) A lesion (tumor or arteriovenous malformation) adjacent to, but not invasive of, the hippocampus, results in the removal of the lesion and adjacent hippocampus in order to ensure a tumor-free margin. This group will be referred to as tumor-related TLE (TTLE) patients. (2) The operation is performed when depth electrode recordings and other evaluative techniques point to the hippocampus as the focus of seizure initiation. This group will be referred to as cryptogenic TLE (CTLE) patients. Analysis of the hippocampi of these two groups of patients reveals that the TTLE hippocampus is quite similar to that of autopsy subjects in its chemical neuroanatomy. However, the dentate gyrus of the CTLE patients shows considerable morphological and cytochemical reorganization. This reorganization is characterized by a number of features. (1) There is a loss of granule cells which occurs either as a patchy loss and/or a thinning of the granule cell layer. (2) Remaining granule cells which contain dynorphin appear to produce recurrent collaterals into the inner molecular layer of the dentate gyrus. (3) In the subgranular region of the hilus (the polymorphic layer) there is a selective loss of interneurons immunoreactive for somatostatin, neuropeptide Y and substance P. (4) There appears to be an increase in fibers immunoreactive for somatostatin and neuropeptide Y which extend throughout the dentate molecular layer. Somatostatin fibers being less numerous than neuropeptide Y fibers (5). The distributions of a number of neurotransmitter receptors also show striking reorganization in the dentate gyrus of the CTLE hippocampus. (6) Second messenger systems protein kinase C and adenylate cyclase, and Na+, K(+)-ATPase activity, as determined by ouabain binding, is increased in the molecular layer of CTLE. This remodeling of the CTLE hippocampus may hold the key to the mechanisms of hyperexcitability of the granule cells in the hippocampus of this group, and consequently the generation of seizures. The removal of the hippocampus in CTLE patients results in good control of seizures, whereas removal of hippocampi that do not show such reorganization, in a group of patients classified as atypical CTLE patients, results in inadequate seizure control. These findings suggest a complex series of processes in converting the properly regulated granule cells into hyperexcitable ones.
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PMID:Neurotransmitters and their receptors in human temporal lobe epilepsy. 136 31

It is now a recognized principle that various neuropeptides are neuronally co-localized with biogenic amine or aminoacid neurotransmitters. In the rat CNS it has previously been shown that TRH is co-localized with 5-HT (and also with substance P) in cell bodies of the posterior raphe that project to the spinal cord. Although TRH cell bodies are known to be widely distributed throughout the forebrain there is no other known co-localization with 5-HT. In this study we further specify the forebrain there is no other known co-localization with 5-HT. In this study we further specify the anatomical relationship of TRH with 5-HT by use of surgical and neurotoxic lesioning with reference to limbic forebrain regions wherein TRH is greatly increased following seizures. In groups of rats, the fimbria-fornix was lesioned alone, or combined with a lesion of the dorsal perforant path or the ventral perforant path. There was a sham lesioned control group. Additional groups were lesioned with 5,7 dihydroxytryptamine, 100 micrograms i.v.t., 45 min. after i.p. desipramine, 25 mg/kg. All rats were sacrificed three weeks after lesions. Indoleamines were determined by HPLC in left anterior cortex, left pyriform/olfactory cortex, left dorsal hippocampus and left ventral hippocampus. TRH was determined by specific RIA in the corresponding right brain regions. The modal n was 7 rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Some regional anatomical relationships of TRH to 5-HT in rat limbic forebrain. 138 39

1. The effects of chemically induced convulsions, clinically similar to those elicited by electroconvulsive treatment (ECT), on brain regional distribution of neuropeptide Y-, neurokinin A-, substance P- and neurotensin-like immunoreactivities were studied in the rat. 2. Pentylenetetrazole (PTZ) and bicuculline (BIC) were used to induce grand mal seizures. Rats were divided into three groups receiving one of the following treatments: Saline, PTZ (45 mg/kg) or BIC (1.5 mg/kg). 3. After sacrifice by focused microwave irradiation, brains were dissected, peptides extracted and measured by specific radioimmunoassays. 4. Repeated grand mal convulsions induced by PTZ, in similarity to ECT, markedly increased NPY-LI concentrations in frontal cortex and hippocampus. In contrast to ECT, no changes in NKA- or SP-LI levels were seen. NT-LI was lowered in striatum. 5. Bicuculline effects were more circumscribed: some animals developed grand mal and died while convulsing (peptides not measured), others did not develop generalized seizures and were sacrificed after the fourth treatment. 6. The results demonstrate a similar effect of PTZ and ECT on regional NPY-LI concentrations and raise the possibility that grand mal, regardless of etiology, is necessary for effects on peptides.
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PMID:Brain neuropeptides: changes by treatment with the convulsants pentylenetetrazole and bicuculline. 149 30

A comprehensive review of the literature on the anatomy, electrophysiology and pharmacology of the substantia nigra is presented. A diagram is developed taking into account the interneuronal interactions of neurotransmitters and receptors that control firing rates and neurotransmitter releases. The central features of the diagram are a positive dopaminergic feedforward process and a positive feedback mechanism mediated by extrasynaptic substance P diffusing from striatal terminals to dopaminergic dendrites of the zona compacta neurons. This loop can enhance the transmission of information from the striatum through the pars reticulata output neurons. The loop is controlled at the level of zona compacta neurons by a negative feedback supported by the dendritic release of dopamine and boosted by pedunculopontine activation mediated by muscarinic receptors. The output of the loop is controlled by two negative feedforward processes, both involving GABAergic striatonigral afferents. Application of the model to pharmacological studies of diverse behaviors including seizures, turning, and conditioned behaviors reveals unforseen relationships and may offer insights into, and directions for, further analysis of the mechanisms and functions involved.
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PMID:Organization and physiology of the substantia nigra. 157 99

Changes in concentrations of the tachykinins substance P, neurokinin A and neurokinin B were investigated in rat brains after kainic acid-induced seizures. Two different antisera, one detecting substance P specifically and one recognizing neurokinins A and B but not substance P, were used. Subsequently to the acute seizures (3 h after kainic acid) significant decreases (by 25-40%) in total neurokinin (A + B) and substance P immunoreactivities were observed in the frontal cortex, dorsal hippocampus and striatum. Depending on the brain area neurokinin immunoreactivity recovered 1-3 days after injection of the toxin and was significantly increased in the frontal cortex (by 40-60%) and the hippocampus (by 100-300%) after 10-60 days. Further analysis by high pressure liquid chromatography revealed that increases in both neurokinin A and neurokinin B concentrations contributed to the increases in total neurokinin immunoreactivity 30 days after kainic acid. At the same time significantly increased levels were also observed for substance P in the frontal cortex (by 30%). Furthermore, increases were also observed in the concentrations of neuropeptide K and gamma-preprotachykinin-A(72-92) in the frontal cortex and the hippocampus 30 days after the kainic acid treatment.
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PMID:Differential changes in tachykinins after kainic acid-induced seizures in the rat. 169 65

Seventy patients aged from one month to 18 years with seizure disorders were classified into three groups: I. Patients who had hard control seizure attacks even under medication; II. those who had occasional seizure attacks (less than 6 times per year) and III. those who had no seizure attacks after receiving medication for at least one year. Blood samples were taken for somatostatin, substance P, prolactin and vasoactive intestinal peptide (VIP) assays. Lumbar puncture was made in 32 children and CSF samples were also assayed for neuropeptides. Somatostatin levels in serum were significantly elevated in group I and group II (P = 0.05, ANOVA) but not in group III and control group. Similar observations were made in substance P, prolactin and VIP studies. In CSF, the somatostation can better indicate the difference between epileptic and normal children (comparison with group I, P greater than 0.001; with group II, P less than 0.001; even with those who were seizure free after medication, P less than 0.05). In conclusion, the levels of several neuropeptides (somatostatin, substance P. prolactin, VIP) were elevated in children with seizure disorders both in serum and CSF. The present investigation provides a new category for the understanding of the pathogenesis, treatment as well as prognosis of seizure disorders.
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PMID:Somatostatin, substance P, prolactin and vasoactive intestinal peptide levels in serum and cerebrospinal fluid of children with seizure disorders. 171 68

Autopsy study of a patient who died after an episode of prolonged unilateral status epilepticus revealed neuronal loss in the hippocampus on the epileptic side, with gliosis confined to the CA1 and CA3 fields. There was loss of the parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)-ergic interneurons in the hippocampus on that side. There was also loss of the normal laminar pattern of substance P staining with increased substance P immunoreactivity in the supragranular plexus on that side. Met-enkephalin immunoreactivity was also increased in the outer molecular layer of the dentate gyrus on the epileptic side. Mossy fibers on the epileptic side stained more strongly with the Hicks' silver stain and with antibodies against glutamate and taurine, but less intensely with antibodies against calbindin. In the contralateral cerebellum, there was Purkinje cell loss, injury to the remaining Purkinje cells, and increased prominence of the Bergmann glia. Our observations show that prolonged unilateral seizure activity can be associated with specific histochemical changes in the human hippocampus.
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PMID:Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus. 171 86

The neuropeptides somatostatin, neurotensin and substance P were investigated in rats during and after limbic seizures induced by systemic injection of kainic acid (10 mg/kg, i.p.). Three hours after injection of the toxin, pronounced decreases (40-50%) in somatostatin-like immunoreactivity in frontal cortex, striatum, dorsal hippocampus and amygdala/pyriform cortex were observed. Concomitantly, neurotensin-like and substance P-like immunoreactivities were also reduced in the frontal cortex and the hippocampus. These early decreases in peptide levels may result from increased release and subsequent inactivation of the peptides during acute seizures. At later time intervals, 3, 10 and 30 days after injection of kainic acid, the initially decreased peptide levels were partially normalized. However, the reduction in somatostatin-like immunoreactivity in amygdala/pyriform cortex and striatum persisted up to 30 days. Neurotensin-like immunoreactivity remained decreased in the frontal cortex. On the other hand, neurotensin- and substance P-like immunoreactivities were increased in the striatum and substantia nigra 10-30 days after injection of kainic acid. These late changes in peptide levels may suggest destruction of peptidergic neurons or adaptive changes induced by the convulsions. Pretreatment of rats with cysteamine (100 mg/kg, i.p.), an agent which decreases brain somatostatin levels, had no effect on the intensity of kainic acid induced convulsions, although a slightly earlier onset of seizures was observed. The changes in peptide levels, especially the marked decreases in somatostatin content after systemic injection of kainic acid, suggest considerable acute and chronic alterations in peptidergic systems caused by limbic convulsions.
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PMID:Kainic acid induced seizures: changes in somatostatin, substance P and neurotensin. 242 20


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