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)

Bilateral intranigral microinfusion of antagonist analogs of substance P significantly attenuated convulsions induced by maximal electroshock or intravenous bicuculline in rats. Infusions of substance P antagonists placed adjacent to the substantia nigra in the vicinity of the lateral hypothalamus were without anticonvulsant action. Our data indicate an as yet undescribed role for substance P antagonists in the regulation of seizure susceptibility, and provide additional evidence that decreasing the activity of substantia nigra outputs is anticonvulsant.
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PMID:Substance P antagonists in substantia nigra are anticonvulsant. 242 45

Recently, several systems of neuropeptides have been demonstrated to have anticonvulsant action in some forms of epilepsy to some extent. However, considerably less knowledge has been taken to their involvement in convulsive disorders either with regard to the development, expression or control of seizures. In this study, therefore, we examined the influence of amygdaloid kindling, an experimental model of temporal lobe epilepsy, on thyrotropin-releasing hormone (TRH), somatostatin (SS), cholecystokinin (CCK) and substance P (SP) content in the amygdala/piriform cortex and hippocampus. Male Sprague-Dawley rats were implanted bipolar electrodes into the left amygdala under pentobarbital anesthesia. Daily kindling stimulation was made to the left amygdala with 1 sec, 60 Hz, 400 microA, until 5 consecutive fully kindled generalized convulsive seizures were elicited. Subsequently, amygdaloid kindled rats were decapitated 30 min, 24 hrs, 48 hrs, 7 days and 21 days after the last amygdaloid stimulation, and the amygdala/piriform cortex and hippocampus were dissected. Control animals only received chronic electrodes, but no stimulation was delivered. The immunoreactivity of TRH, SS, CCK and SP was examined by methods of specific radioimmunoassay. The TRH content in these two brain regions significantly increased 24 hrs after the last kindled convulsion. This increase became maximal 48 hrs after the last convulsion: about 3-fold and 4-fold of the control in the amygdala/piriform cortex and hippocampus, respectively. Such increases in the TRH content tended to persist for 7 days, but returned to the control level 21 days after the last convulsion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of amygdaloid kindling on thyrotropin-releasing hormone, somatostatin, cholecystokinin and substance P contents of the amygdala/piriform cortex and hippocampus of rats]. 246 12

Chronically implanted rats were injected either with somatostatin (SST) lumbar intrathecally (i.t.) (100 micrograms, n = 5), into the fourth ventricle (3 micrograms, n = 5; 10 micrograms, n = 6; 30 micrograms, n = 5) or into the lateral ventricle (10 micrograms, n = 6; 30 micrograms, n = 6), or received an injection of the substance P (SP) analogue, [D-Pro2, D-Trp7,9]SP into the fourth ventricle (0.3 micrograms, n = 2; 1 micrograms, n = 4; 3 micrograms, n = 4; 10 micrograms, n = 1) or lateral ventricle (3 micrograms, n = 3). A dose-dependent EEG depressant effect was observed following fourth and lateral ventricular injections of SST and of the SP analogue. Acute death due to respiratory depression was observed following i.t. and fourth ventricular injection of SST, and fourth ventricular injection of the SP analogue. Prominent motor behavior (barrel rotation, circling, cranial stereotypies) was observed, without signs of EEG seizure activity, following intraventricular injection of both drugs. Present findings indicate neurotoxic effects of SST and SP analogue at the cerebral level.
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PMID:Electroencephalographic and behavioral assessment of intracerebroventricular somatostatin and a substance P analogue. 247 57

The goal of this study was to examine vascular responses of the dura mater. Microspheres were used to measure blood flow to the dura and brain in anesthetized dogs. Under control conditions, blood flow to the dura was 38 +/- 3 (SE) ml.min-1.100 g-1. Values for blood flow to the dura obtained with simultaneous injection of 15- and 50-microns microspheres were similar, which suggests that shunting of 15-microns spheres was minimal. Left atrial infusion of substance P (100 ng.kg-1.min-1) and serotonin (40 micrograms.kg-1.min-1), two agonists that have been reported to increase vascular permeability in the dura, increased blood flow to the dura two- to threefold. Adenosine (iv) produced vasodilatation in the dura. Adenosine and serotonin did not affect cerebral blood flow, but substance P increased blood flow to the brain by approximately 40%. Seizures, which produce pronounced dilatation of cerebral vessels despite activation of sympathetic nerves, produced vasoconstriction in the dura. Thus 1) the dura is perfused at a relatively high level of blood flow under normal conditions and is very responsive to vasoactive stimuli, and 2) substance P and serotonin, which have been implicated in the pathogenesis of vascular headache, produce pronounced vasodilator responses in the dura mater.
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PMID:Vascular responses of dura mater. 247 56

A cholinergic projection from the dorsolateral tegmentum to the medial anterior cortex has previously been shown to contain substance P and corticotropin releasing factor. Behavioral analysis of acetylcholine, substance P and corticotropin releasing factor microinjected into the medial anterior cortex revealed a seizure-related "boxing" behavior elicited by carbachol, which was potentiated by coinjection with substance P and antagonized by coinjection with corticotropin releasing factor. We now report that two antagonists of substance P receptors, [D-Pro2, D-Phe7, D-Trp9]-substance P and [D-Pro2, D-Trp7,9]-substance P, attenuate "boxing" behavior when coinjected with carbachol. Neither antagonist produced observable behavioral effects when microinjected alone. An analog of substance P, [pGlu,5, MePhe,8 Sar9]-substance P (5-11) potentiated carbachol-induced "boxing" at doses similar to naturally-occurring substance P. Monoclonal and polyclonal antisera against substance P were not effective antagonists of carbachol-induced "boxing." The ability of substance P antagonists to block carbachol-induced "boxing" has two major implications: (1) endogenous substance P may be modulating endogenous acetylcholine in the tegmental-cortical pathway; and (2) substance P antagonists may provide a new avenue for the development of antiepileptic drugs.
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PMID:Substance P antagonists block carbachol-induced "boxing" behavior at a site of coexistence in the rat prefrontal cortex. 248 49

The substantia nigra has been identified as a critical site at which gamma-aminobutyric acid (GABA) agonist drugs act to reduce susceptibility to a number of types of experimentally induced generalized seizures. Moreover, the ability of systemically administered GABA-elevating agents to protect against maximal electroshock seizures is directly correlated with an increase in GABA specifically in the nerve-terminal compartment of substantia nigra. The significance of these findings is discussed in terms of the role of specific nigral synapses for the control of seizure propagation. Evidence from lesion studies, as well as studies with opiates and substance P analogs, further supports the hypothesis that Inhibition of nigral efferents reduces susceptibility to generalized seizures. Inhibition of nigral outflow causes a decreased sensitivity to chemoconvulsants without precluding the animal's ability to exhibit any or all of the motor components of a seizure. We therefore propose that nigral outputs are capable of facilitating seizure propagation and can function as a gating mechanism for the generalization of convulsive activity.
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PMID:Mechanisms of seizure control mediated by gamma-aminobutyric acid: role of the substantia nigra. 298 54

The relationship between cerebral GABA content and susceptibility to seizures is addressed from the point of view of specific brain loci at which GABA synapses may control convulsive activity. The substantia nigra (SN) has been identified as a critical site at which GABA-agonist drugs act to reduce susceptibility to a number of types of experimentally induced generalized seizures. Moreover, the ability of GABA-elevating agents to protect against seizures in the maximal electroshock model is directly correlated with increases in GABA specifically in the nerve-terminal compartment of SN. Studies with 2-deoxyglucose indicate that a marked increase in metabolic activity in SN is a common feature of several types of generalized seizures; it is possible that some of this increased activity is associated with GABAergic nerve terminals that become activated in an attempt to suppress seizure spread. Because GABA has been shown to inhibit nigral efferents, it is likely that GABA terminals inhibit nigral projections that are permissive or facilitative to seizure propagation. In support of this, bilateral destruction of SN attenuated clonic and tonic chemoconvulsant and electroshock seizures. Other treatments capable of reducing nigral output, namely opiate agonists (morphine and D-Ala-Met-enkephalin), and substance P antagonist analogs, were also found to have anticonvulsant effects when applied bilaterally into SN. Thus, the seizure-facilitating nigral efferents may be subject to inhibition by both GABA and opiates and may normally be driven by substance P. Of the various outputs from SN, the GABAergic projections to thalamus, reticular formation and/or superior colliculus are most likely responsible for influencing seizure propagation. Experimental evidence does not indicate a significant role of pars compacta nigrostriatal dopamine neurons for controlling the various types of seizures subject to nigral influence. We propose that the inhibition of the GABAergic outputs from SN pars reticulata can suppress the progression of seizure discharge through circuits involving the target areas of these outputs. Because chemical or electrical stimulation of SN does not initiate convulsions, it appears that seizure activity generated elsewhere in the brain may be amplified or sustained by activity in these nigral outputs.
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PMID:Role of the substantia nigra in GABA-mediated anticonvulsant actions. 301 Jun 76

High amplitude spiking representative of seizures, accompanied by an unusual motor behavior pattern of rearing and forelimbic clonus resembling "boxing," was elicited by microinjection of the cholinergic agonist, carbachol, 4 micrograms, into the medial prefrontal cortex of the rat. A rating scale devised to score the behavior revealed a motor pattern elicited by carbachol from the medial anterior cortex which was similar to that described by Racine for electrical stimulation of the amygdala. Topographical analysis of the areas surrounding the medial anterior cortex region revealed that the motor manifestations of seizures were elicited over a wide region of the anterior cortex, with scores significantly lower at carbachol microinjection sites greater than 1 mm rostral, 2 and 3 mm caudal, and 2 mm lateral to the standard medial prefrontal cortex site. Unilateral microinjection of carbachol yielded motor seizures primarily from the contralateral forepaw, suggesting involvement of a crossed pathway. Retrograde tracing with fast blue dye, combined with immunostaining for choline acetyltransferase and NADPH-diaphorase, found that the cholinergic neurons innervating the standard microinjection site were the dorsolateral tegmental cells, as previously reported, which have been shown to also contain substance P and corticotropin releasing factor. In addition, cholinergic neurons of the nucleus basalis of Meynert region were found to innervate the standard microinjection site. These findings implicate cholinergic innervation of the rostral cortex in classical limbic seizures.
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PMID:Anatomical analysis of frontal cortex sites at which carbachol induces motor seizures in the rat. 317 34

The onset of therapeutic effectiveness of carbamazepine is generally very rapid in the treatment of seizure and paroxysmal pain disorders, shows some lag in the treatment of mania, and exhibits the longest lag in depression. These time course variations may indicate that different mechanisms underlie the efficacy of carbamazepine in the differential neuropsychiatric syndromes. Biochemical and pharmacological data suggest that the anticonvulsant effects of carbamazepine are related to "peripheral-type" benzodiazepine and alpha 2-noradrenergic receptor systems and to its ability to stabilize sodium channels. GABAB (baclofen-like) actions appear to be involved in antinociceptive, but not anticonvulsant, effects. The relatively acute time course of antimanic efficacy may be related to the above-mentioned mechanisms or to other effects related to systems postulated to be altered in the manic syndrome. These effects might include carbamazepine's ability to increase acetylcholine in the striatum, decrease probenecid-induced levels of CSF homovanillic acid (HVA) in man and dopamine turnover in animals, decrease CSF norepinephrine in manic patients, inhibit adenylate cyclase activity (in response to norepinephrine, dopamine, adenosine, or ouabain), decrease GABA turnover, or act as a vasopressin agonist. Efficacy in depression may be related to actions in man that take time or chronic drug administration to develop, such as increases in plasma tryptophan, decreases in CSF somatostatin, decreases in thyroid indices, and increases in urinary free cortisol excretion and, in animals, increases in substance P sensitivity and increases in brain adenosine receptors. The ability of carbamazepine to block the development of lidocaine- and cocaine-induced seizures also requires chronic administration, suggesting that these seizure models may provide a unique perspective for understanding mechanisms of time-dependent effects.
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PMID:Time course of clinical effects of carbamazepine: implications for mechanisms of action. 328 May 60

Subcutaneous post-trial administration of the neuropeptide substance P was found to reverse the amnestic effects of both electroconvulsive shock and cycloheximide. Substance P was observed to reverse the amnestic effects of cycloheximide in both C57B1/6J and heterogeneous strain (HS) mice. Substance P was found to reverse the amnestic effects of electroconvulsive seizures in C57B1/6J animals. Peripheral injections of substance P were also found to facilitate the retention of a single-trial passive avoidance habit in animals of both genotypes, provided a weak footshock was used during training.
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PMID:Substance p reversal of electroconvulsive shock and cycloheximide-induced retrograde amnesia. 619 65


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