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)

Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N'-(DL-SERYL)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine. Substance P appears to stimulate monoaminergic neurons in the brain and to serve as an excitatory transmitter in nerve terminals impinging upon dopaminergic cell bodies. A similar stimulation of noradrenaline and 5-hydroxytryptamine indicate a similar transmitter role for noradrenergic and serotonergic neurons. These data strengthen questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia.
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PMID:Effect of synthetic substance P on monoaminergic mechanisms in brain. 0 76

The present work was carried out to observe the effect of intra-cerebroventricular (icv) injection of monoamine neurotransmitters, enkephalin and morphine on immunoreactive substance P(Ir-SP) contents in hypothalamus, striatum, hippocampus and pain threshold. The results were as follows: (1) After icv or intra-DR (dorsal raphe nucleus) injection of 5-HTP, the content of Ir-SP in hypothalamus significantly decreased and pain threshold markedly increased; After depletion of the 5-HT content in brain by pCPA or destruction of DR, the contents of Ir-SP were remarkably elevated in three brain regions by the former and in hypothalamus, striatum by the later. (2) The Ir-SP levels in the three brain regions and the pain threshold were not affected by the icv injection of NE, however, icv injection of DA caused a increase of Ir-SP concentration in striatum which was reversed by the DA receptor antagonist haloperidol, but without any change of the pain threshold. 7th day after icv injection of 6-OHDA, the content of Ir-SP in striatum significantly reduced. (3) Icv injection of met-enkephalin (MEK) or morphine could increase the Ir-SP levels in hypothalamus, striatum and the pain threshold, and above-mentioned effect of morphine could be prevented by the opioid receptor antagonist naloxone. Icv injection of leu-enkephalin (LEK) had no effects both on Ir-SP contents in three brain regions and the pain threshold.
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PMID:[Effect of monoamine neurotransmitters, enkephalin and morphine on substance P contents of several brain regions and pain threshold in rats]. 170 64

In the present work we examined the effect of the neutralization of endogenous substance P by the administration of an anti-substance P serum (ASPS) on GABA concentration in the anterior pituitary in hyperprolactinemic conditions induced by 5-hydroxytryptophan or by grafting anterior pituitaries. ASPS reduced the increase in the anterior pituitary GABA concentration induced by hyperprolactinemia. In vitro experiments showed that substance P inhibited K(+)-evoked GABA efflux from hypothalamic fragments and decreased GABA concentration in the anterior pituitary but ASPS increased it. Our results demonstrate that substance P modifies hypothalamic GABA release and anterior pituitary GABA concentration and suggest that an interaction exists between substance P and GABA.
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PMID:Substance P affects the GABAergic system in the hypothalamo-pituitary axis. 170 34

The bowel is the only organ of the body in which neural reflexes can be elicited in the absence of input from the brain or spinal cord. This activity is mediated by the enteric nervous system (ENS), which contains primary afferent neurons. Experiments were carried out to locate the primary afferent neurons of the ENS. Two types of stimulation were used to activate neurons in the wall of the gut in vitro: exposure of the mucosa to cholera toxin or delivery of pressure to the mucosal surface with puffs of N2 from a micropipette. Neurons that became active in response to these stimuli were identified by demonstrating the intranuclear immunoreactivity of Fos, the product of the c-fos protooncogene. No Fos immunoreactivity could be detected in the absence of stimulation; however, application of cholera toxin and puffs of N2 each induced the appearance of Fos immunoreactivity in neurons in both the submucosal and myenteric plexuses. With either stimulus, the induction of Fos immunoreactivity was antagonized by TTX and therefore depended on neuronal activity. The appearance of Fos immunoreactivity could also be prevented by the 5-HT1P receptor antagonist N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide. In contrast, the stimulus-induced expression of Fos immunoreactivity was inhibited, but not abolished, by hexamethonium, which limited the spread of activation within the submucosal plexus and completely prevented expression of Fos immunoreactivity by myenteric neurons in response to mucosal puffs of N2. FluoroGold was injected into single ganglia of the myenteric plexus in order to identify submucosal neurons with myenteric projections. Submucosal neurons in which Fos immunoreactivity was induced by the stimuli were doubly labeled by FluoroGold. A subset of the submucosal, but not myenteric, neurons that expressed Fos immunoreactivity was doubly labeled by antibodies to calbindin. Submucosal calbindin-immunoreactive neurons were found to contain substance P immunoreactivity and could also be immunostained by anti-idiotypic antibodies that react with 5-HT1P receptors. A subset of dynorphin1-8-immunoreactive submucosal neurons (which are known to costore vasoactive intestinal peptide and to be secretomotor in function) expressed nuclear Fos immunoreactivity in response to cholera toxin, but not puffs of N2. These data suggest that intrinsic primary afferent neurons are located in the submucosal plexus, project to the myenteric plexus, and are activated by 5-HT acting on the 5-HT1P receptor subtype. These neurons are probably cholinergic and costore calbindin and substance P.
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PMID:Identification and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity. 172 36

The carcinoid syndrome can arise when effluent blood from carcinoid tumor tissue gains access to the systemic, as opposed to the portal, venous system. Features include facial flushing, diarrhea, wheezing, right-sided cardiac lesions, and retroperitoneal fibrosis. Attacks of flushing, diarrhea, and wheezing can be provoked by bolus injections of adrenaline, noradrenaline, or pentagastrin. While serotonin usually predominates, carcinoid tumors can also secrete, in varying proportions, 5-hydroxytryptophan, kallikrein, kinins, substance P and other neuropeptides, prostaglandins, catecholamines, and histamine. Of these, serotonin, kinins, histamine, and substance P are possible mediators of flushes; serotonin and substance P of hyperperistalsis; and serotonin, kinins, or histamine of bronchial constriction. Despite the gross excess of circulating serotonin, nearly all is platelet bound and therefore inactive. Very little is free in plasma. Demonstration of a contribution of serotonin to carcinoid attacks requires assay of free plasma serotonin; measurements of whole blood or serum serotonin are of little value. Some, but not all, provoked flushes have been shown to be accompanied by a rise in free plasma serotonin or substance P; an increase in circulating kinins has been more consistently shown. The 5HT2 antagonist ketanserin has been found to inhibit both provoked and spontaneous attacks of flushing, diarrhea, and dyspnea in a proportion of patients with carcinoid syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carcinoid syndrome and serotonin: therapeutic effects of ketanserin. 228 51

Substance P, administered intrathecally in the lumbar area of paraplegic rats activated the electromyogram (EMG) of the hindlimbs. This effect was markedly enhanced by previous denervation by 5,7-dihydroxytryptamine. Stimulation of the motoneurons by substance P was followed by a blunted response to the excitatory substances thyrotropin releasing hormone (TRH) and 5-hydroxytryptophan (5-HTP), given intraperitoneally 1 hr later. The decreased sensitivity to 5-HTP persisted for more than 24 hr. In several animals, however, a flaccid paralysis was observed after administration of substance P. In such cases the response to 5-HTP was enhanced 24 hr later. These observations suggest an interaction between 5-HT, TRH and substance P in the control of the excitability of motoneurons.
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PMID:Substance P in the lumbar spinal cord of the rat affects the motor response to 5-HTP and TRH. 242 10

We have investigated the influence on the excitability of lumbar motoneurons of 5-hydroxytryptamine (5-HT), substance P and thyrotropin releasing hormone (TRH), three substances which coexist in the same bulbospinal descending pathway and end in large part around motoneurons. We have also studied the effect of clonidine, an alpha 2 noradrenergic agonist. This was done in spinalized rats (T5) treated three weeks before with 5-7-dihydroxytryptamine. Under those circumstances 5-HTP (I.P.), 5-HT (intrathecally) TRH (I.P. or I.T.) and substance P (I.T.) all elicited a strong excitation of motoneurons as measured by integrated EMG of the hindlimb muscles. Substance P reduced by almost half the subsequent response to 5-HTP, 1 hour and 24 hours later. TRH given acutely did not modify the response to 5-HTP but given chronically for twenty one days by means of Alzet minipump, markedly increased the response to 5-HTP. Clonidine by itself decreased the excitability of motoneurons and antagonized the excitatory effect of 5-HTP and TRH. In a pilot trial, cyproheptadine, a 5-HT antagonist was shown to decrease the manifestations of spasticity in patients with a partial spinal lesion. Clonidine also appears to be of potential use in the treatment of spasticity.
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PMID:Action of 5-hydroxytryptamine, substance P, thyrotropin-releasing hormone and clonidine on motoneurone excitability. 244 57

The effects of the acute injection of a rabbit anti-substance P serum (ASPS) were studied in normal rats and rats with hyperprolactinemia induced by 5-hydroxytryptophan and estradiol given as a short or chronic treatment. The anti-substance P serum decreased the release of prolactin induced by 5-hydroxytryptophan when this serotonin precursor was injected 24 h, but not 1 h, after the administration of the antiserum. ASPS reduced the hyperprolactinemia induced by short and chronic treatment with estradiol in castrated rats. This effect was observed 24 h after the injection of the antiserum. On the other hand, the injection of ASPS induced a significant decrease in LH levels in serum of intact male rats injected with 5-hydroxytryptophan 24 h after ASPS, and in castrated rats treated with short-term and chronic administration of estradiol, 24 h after the injection of the antiserum. These results suggest that substance P may have a role in the control of prolactin secretion and could play a part in the hyperprolactinemic effects of estradiol. On the other hand, substance P, under certain circumstances, may stimulate LH release.
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PMID:Effect of an anti-substance P serum on prolactin and gonadotropins in hyperprolactinemic rats. 244 53

Two types of 5-hydroxytryptamine (5-HT) receptor, 5-HT1P and 5-HT3, have been identified physiologically on enteric neurons impaled by intracellular microelectrodes. Activation of 5-HT1P receptors evokes a long-lasting membrane depolarization associated with an increased input resistance, whereas stimulation of 5-HT3 receptors results in a brief depolarization during which the input resistance falls. Slow excitatory postsynaptic potentials (EPSPs) in myenteric type II-hyperpolarizing afterpotential (AH) neurons have been demonstrated to be mediated by 5-HT1P receptors. The current experiments were done to determine whether the substituted benzamide, BRL 24924, is a specific antagonist at 5-HT1P receptors and can be used as a probe to investigate the role played by serotoninergic neurons in the control of gastrointestinal motility. Intracellular microelectrodes were used to analyze the effects of BRL 24924 on guinea pig myenteric neurons. Microejection of BRL 24924 mimicked neither the long-lasting nor the brief response to 5-HT; however, BRL 24924 (0.5-1.0 microM) reversibly antagonized both the long-lasting 5-HT1P receptor-mediated responses of myenteric neurons to 5-HT and 5-HT-mediated slow EPSPs. A greater than 10-fold higher concentration of BRL 24924 was required to reduce the short-lived responses mediated by 5-HT3 receptors. BRL 24924 did not affect the response of myenteric neurons to substance P. These results indicate that BRL 24924 is primarily a 5-HT1P antagonist. Unlike other 5-HT1P agonists or antagonists, BRL 24924 did not block the binding of 5-[3H]HT to 5-HT1P receptors. This observation suggests that specific antagonism of physiological responses to 5-HT by BRL 24924 may be the result of an action on the coupling of the 5-HT1P receptor to its effector mechanism. BRL 24924 (0.5-1 mg/kg) and another 5-HT1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5 mg/kg), significantly increased the rate of emptying of a 51Cr-labeled liquid meal from the murine stomach. In contrast, the 5-HT3 antagonist, ICS 205-930 (0.1-0.5 mg/kg), did not affect the rate of gastric emptying. These observations are consistent with the hypothesis that intrinsic inhibitory neurons of the murine stomach are activated by serotoninergic axons acting through 5-HT1P receptors. Antagonism of an excitatory drive to neurons in a relaxant pathway may thus explain the gastrokinetic effects of BRL 24924.
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PMID:Blockade of 5-HT-mediated enteric slow EPSPs by BRL 24924: gastrokinetic effects. 278 10

The authors describe the anatomical features and physiological properties of central serotonergic neurons. The central serotonin neurons (part of which store peptides [substance P, TRF, enkephalins] in addition to 5HT) are highly collateralized reticular-type brain stem neurons receiving multi-modal afferent information from ascending sensory and descending motor pathways. They are under control by noradrenergic, peptidergic and and gaba-ergic projection neurons and interneurons. Furthermore, they establish variable synaptoid and synaptic contacts to neuronal, glial and secretory targets throughout the entire neuraxis and send terminal branches into the ventricular CSF space. Firing rate and transmission activity appear to be controlled in a complex and rather rigid manner by 5HT release-dependent dendrodendritic and dendrosomatic inhibition via autoreceptors (which also regulate release at the axon terminals) and via transsynaptic inhibitory feedback circuits which may involve gabaergic projection and interneurons. 3H-imipramine appears to bind to an "imipramine recognition site" in the vicinity of the 5HT carrier, and to a variety of other transport and (postsynaptic) receptor sites (NA uptake, H1, 5HT2- and alpha 1-binding sites). Circumstantial evidence points to an as yet undetermined role of the postsynaptic 5HT-1-binding sites in neurotransmission. 5HT-2-binding sites fulfil the criteria for receptors: binding affinity of antagonists to these sites correlates significantly with their potency to inhibit behavioral excitation in rats elicited by 5-hydroxytryptophan or 5HT agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anatomical features and physiological properties of central serotonin neurons. 299 53


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