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)

We investigated the influence of four substances on the excitability of lumbar motoneurons. These substances, three of which coexist in the same bulbospinal descending pathways that end, for the most part, around motoneurons (MNS), are: 5-hydroxytryptamine (5-HT), substance P (SP) and thyrotropin-releasing hormone (TRH). We also studied the effects of clonidine, an alpha 2 noradrenergic (NA) agonist. This study was carried out in rats spinalized at T5 and treated three weeks earlier with 5-7 dihydroxytryptamine (5-7 DHT). Under these conditions, the following responses were observed: 5-HTP (5-HT precursor) intraperitoneally (I.P.), 5-HT intrathecally (I.T.), TRH (I.P. or I.T.) and substance P (I.T.) all elicited strong excitation of MNS as measured by integrated EMG of the hindlimb muscles; substance P reduced by almost half the response to 5-HTP given one hour and 24 hours later; TRH given acutely did not modify the response to 5-HTP, but given chronically for 21 days markedly increased the response to this substance. Clonidine by itself decreased the excitability of MNS and antagonized the excitatory effects of 5-HTP and TRH. In two separate pilot trials, cyproheptadine, a 5-HTP antagonist, decreased the manifestations of spasticity in a patient with a partial spinal lesion. It would appear that clonidine may have potential use in the management of spasticity.
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PMID:Action of 5-hydroxytryptamine, substance P, thyrotropin releasing hormone and clonidine on spinal neuron excitability. 754 99

JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)-1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific inhibitor of prolyl endopeptidase (PEP). JTP-4819 (3 mg/kg p.o.) exhibited a strong and durable ex vivo inhibitory effect on PEP in various regions of the rat brain. In addition, JTP-4819 inhibited the degradation of substance P, arginine-vasopressin, thyrotropin-releasing hormone, neurotensin, oxytocin, bradykinin, and angiotensin II by purified PEP with IC50 values of 9.6, 13.9, 10.7, 14.0, 4.5, 7.6 and 10.6 nM, respectively. In the one-trial passive avoidance test in rats with scopolamine-induced amnesia, JTP-4819 significantly prolonged the retention time when administered orally at doses of 1 and 3 mg/kg 1 hr before acquisition or at 3 and 10 mg/kg 1 hr before retention. In addition, coadministration of JTP-4819 and substance P, arginine-vasopressin or thyrotropin-releasing hormone (at doses at which each drug alone did not prolong the retention time) improved the retention time of rats with scopolamine-induced amnesia. Microdialysis studies demonstrated that JTP-4819 caused a significant increase in ACh release in the frontal cortex and hippocampus of young rats at oral doses of 1 and 3 mg/kg, as well as in both brain regions of aged rats at a dose of 3 mg/kg. These results indicate that JTP-4819 potentiates neuropeptide functions inhibiting PEP, that it activates cholinergic transmission and that it enhances learning and memory.
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PMID:JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive enhancer. 756 10

This study investigated possible sites of contact of nerve fibers containing a range of putative neurotransmitter substances onto neurons in the cat ventral medulla oblongata concerned with autonomic, particularly cardiovascular, regulation. The parasympathetic preganglionic neurons of the nucleus ambiguous (correction of ambiguus) were identified by retrograde horseradish peroxidase tracing from the vagus nerve, and the groups of neurons in the A1 and C1 cell areas and the raphe nucleus by catecholamine enzyme or 5-hydroxytryptamine (5-HT) immunohistochemistry, respectively. Immunoreactive (-ir)nerve fibers and terminals in the vicinity if these neurons were visualized by subjecting the sections to a dual-staining technique using a brown peroxidase-diaminobenzidine reaction product and a blue alkaline phosphatase-Fast blue reaction product. By employing monochrome photography with combinations of blue and orange-red filters, it was possible to discriminate neural elements displaying one or the other reaction product, or colocalization of reaction products. The results revealed the presence of calcitonin gene-related peptide (CGRP) and galanin (GAL)-ir in some motoneurons of the nucleus ambiguus, but not in those innervating the heart via the cardiac vagus nerve. The latter group of parasympathetic efferent neurons were found to be densely innervated by fibers immunoreactive for dopamine beta-hydroxylase (DBH, indicating noradrenaline), glycine (GLY), gamma-aminobutyric acid (GABA), 5-HT, enkephalin (ENK), neuropeptide Y (NPY), substance P (SP), and thyrotropin-releasing hormone (TRH), and, to a lesser extent, by other neuropeptide-ir fibers. The catecholamine cells of the rostral C1 and caudal A1 groups showed a broadly similar pattern of innervation, most noticeably by fibers immunoreactive for DBH, GABA, 5-HT, cholecystokinin (CCK), CGRP, ENK, GAL, NPY, and SP. The 5-HT-ir neurons of the raphe nucleus, some also containing SP, TRH, ENK, or corticotropin-releasing factor (CRF)-ir, were most prominently innervated by terminals containing DBH, GABA, CCK, ENK, NPY, TRH, somatostatin (SRIF), and vasoactive intestinal polypeptide (VIP)-ir. Although the proof that these groups of neurons receive functional synaptic contacts from the immunoreactive fibers awaits further ultrastructural studies, the results do suggest that a wide range of putative transmitters may influence the activity of efferent neurons in the cat medulla controlling autonomic functions.
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PMID:Immunolocalization of putative neurotransmitters innervating autonomic regulating neurons (correction of neurones) of cat ventral medulla. 763 97

The functional role of thyrotropin-releasing hormone (TRH) at the lower esophageal sphincter (LES) was examined in the cat. The specific aims of this study were to determine: 1) the relative distribution of TRH throughout the feline gastrointestinal tract and 2) the effect of TRH on LES basal pressures and its response to exogenously induced contractions. TRH concentrations were determined by radioimmunoassay in tissue extracts from 12 sites. The mean concentration of TRH at the manometrically determined LES was 240 +/- 85 pg/g wet wt tissue, and the maximal concentration was just distal to the LES (659 +/- 189 pg/g wet wt). TRH concentration was higher in the mucosa than the underlying muscle layer of the fundus, antrum, duodenum, and ileum. In physiological studies, TRH given selectively via the left gastric artery had no effect on basal LES or esophageal pressures. TRH (2.8 x 10(-8) mol/kg) decreased the LES response to the D50 of substance P by 47.2% (34.8 +/- 3.1 to 18.4 +/- 2.9 mmHg, P < 0.01). In the presence of tetrodotoxin, TRH gave a similar inhibition of substance P-induced contractions (53.5%). TRH also decreased bombesin-induced contractions by 47.5% (29.6 +/- 6.0 to 15.8 +/- 3.9 mmHg, P < 0.025). TRH, however, had no effect on bethanechol-induced contractions. We conclude that 1) TRH is present throughout the gastrointestinal tract, with highest concentrations in the region distal to the LES; 2) TRH has no effect on basal LES tone; and 3) TRH inhibits the LES response to endogenously released and exogenous substance P but not the LES response to bethanechol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyrotropin-releasing hormone: an inhibitory regulatory peptide of feline lower esophageal sphincter. 768 29

The actions of substance P and thyrotropin-releasing hormone (TRH) on neonatal rat spinal motoneurones in vitro were compared using intracellular current and voltage clamp techniques. Like TRH, substance P evoked a slowly-developing, persistent depolarisation plus an increase in input resistance under current clamp conditions. Under voltage clamp conditions, substance P elicited an inward current (mainly due to a conductance block) which peaked near -40 mV and reversed polarity close to the estimated EK. A distinct conductance increase (with a reversal potential near zero) also appeared to contribute to this response. The response to substance P at resting potential was suppressed by 1.5 mM Ba2+, but not by 20 mM tetraethylammonium, 2 mM 4-aminopyridine, 2 mM Cs+ and 0.2 mM Cd2+. In addition, co-application of TRH and substance P mutually occluded each other. Thus, it is suggested that substance P and TRH share a common effector mechanism, which primarily involves the suppression of IK(T), a persistent K+ current recently discovered in these neurones.
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PMID:Substance P and TRH share a common effector pathway in rat spinal motoneurones: an in vitro electrophysiological investigation. 768 7

The spinal cord is innervated by brainstem serotonergic neurons, some of which contain substance P and/or thyrotropin-releasing hormone in addition to serotonin. These neurons project at least three types of axons to the spinal cord: those containing both substance P and thyrotropin-releasing hormone, those containing thyrotropin-releasing hormone but not substance P, and those containing neither substance P nor thyrotropin-releasing hormone. However, the organization of the different types of serotonergic processes is unclear. In the present studies, the types of serotonergic axons projecting to two kinds of spinal neurons were examined. Somatic and parasympathetic preganglionic motoneurons were labeled retrogradely from the pelvic or sciatic nerve, respectively. Sections containing these neurons were stained either for serotonin and substance P, or for serotonin and thyrotropin-releasing hormone. Of a total of 428 profiles examined that were retrogradely labeled from the sciatic nerve, 425 (99%) were apposed by serotonin-immunoreactive varicosities; similarly, of a total of 382 profiles examined that were retrogradely labeled from pelvic nerve, 353 (92%) were apposed by serotonin-immunoreactive varicosities. However, differences appeared to exist between the types of serotonergic varicosities innervating these two groups of neurons. Among the profiles labeled from the sciatic nerve, it was estimated that over 97% were apposed by serotonin-immunoreactive varicosities in which serotonin co-existed with substance P and thyrotropin-releasing hormone. In contrast, among the profiles labeled from pelvic nerve that were apposed by serotonin-immunoreactive varicosities, it was estimated that less than 1% were apposed by serotonin-immunoreactive varicosities containing both thyrotropin-releasing hormone and substance P. We estimate that most of the remainder (about 80%) were apposed by serotonin-immunoreactive varicosities containing thyrotropin-releasing hormone but not substance P. We conclude that both the cell bodies of neurons retrogradely labeled from the pelvic nerve and those labeled from the sciatic nerve were apposed by serotonin varicosities. However, these two systems of neurons appear to be innervated largely by two different populations of serotonergic cells. This suggests that the raphe-spinal serotonergic system may independently modulate the activities of somatic motoneurons and parasympathetic preganglionic motoneurons.
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PMID:Organization of the serotonergic innervation of spinal neurons in rats--III. Differential serotonergic innervation of somatic and parasympathetic preganglionic motoneurons as determined by patterns of co-existing peptides. 768 80

Little is known about the functional role of putative neurotransmitters in the nucleus raphe obscurus (NRO) in the control of gastric motor function, although thyrotropin-releasing hormone (TRH) and substance P (SP) have been detected in the cell bodies and/or fibers of this nucleus. Therefore, we investigated the effects of microinjection of these peptides (in a volume of 60 nl) into the caudal NRO of alpha-chloralose-anesthetized rats while recording intragastric pressure, pyloric and greater curvature motility, and blood pressure. L-Glutamate (30 nmol) was first microinjected into the NRO to identify the "gastric" region of the NRO and elicited significant increases in intragastric pressure as well as pyloric and greater curvature motility in all 16 animals. TRH (2-45 pmol, n = 16) microinjected into the same sites increased intragastric pressure as well as pyloric and greater curvature motility, and these effects were abolished by bilateral cervical vagotomy and atropine (0.5-1.0 mg/kg iv) but not by spinal cord transection. Microinjection of SP (45-405 pmol, n = 15) into the same sites decreased intragastric pressure; however, the inhibitory effect of SP on pyloric and greater curvature motility did not attain statistical significance. The effect of SP on intragastric pressure was completely abolished by bilateral vagotomy but not by systemic administration of atropine (1 mg/kg) or spinal cord transection. Microinjections of 45 pmol TRH and 405 pmol SP just outside of the NRO did not result in changes in gastric function. No overall significant changes in blood pressure were noted after microinjection of L-glutamate, TRH, or SP into the gastric region of the NRO. We conclude that both TRH and SP affect gastric motor function in the caudal NRO via a vagally mediated pathway; TRH apparently activates vagal cholinergic pathways, but the mechanism of SP-evoked gastric motor inhibition remains to be further investigated.
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PMID:Opposing gastric motor responses to TRH and substance P on their microinjection into nucleus raphe obscurus of rats. 769 1

The role of calcitonin gene-related peptide (CGRP) in the vagal cholinergic-mediated increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analogue RX-77368 injected intracisternally (ic, 30 ng) was investigated in urethan-anesthetized rats using the hydrogen gas clearance technique. alpha-CGRP (14 micrograms.kg-1.h-1) or bethanechol (150 micrograms.kg-1.h-1) infused close intra-arterially to the stomach or RX-77368 injected intracisternally increased GMBF by 76, 102, and 131%, respectively, 30 min after administration. The CGRP antagonist, human CGRP-(8-37) [hCGRP-(8-37)], injected intravenously (15 micrograms/kg bolus and 3 micrograms.kg-1.h-1) inhibited by 100, 97, and 73% the gastric hyperemic response to alpha-CGRP, TRH analogue, and bethanechol, respectively, whereas the substance P antagonist CP-96,345 (3 mg/kg iv) had no effect. In capsaicin-pretreated rats, hCGRP-(8-37) no longer blocked the increase in GMBF induced by intracisternal RX-77368. These results suggest that the gastric hyperemic response to central vagal activation induced by intracisternal TRH analogue at 30 ng is mediated by local effector function of capsaicin-sensitive afferent fibers releasing CGRP.
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PMID:Central vagal activation by TRH induces gastric hyperemia: role of CGRP in capsaicin-sensitive afferents in rats. 781 Jun 51

The distribution of twelve biologically active neuropeptides, i.e., thyrotropin-releasing hormone, corticotropin-releasing factor, pro-opiomelanocortin-derived peptides (adrenocorticotropic hormone, beta-endorphin, alpha-melanocyte-stimulating hormone), leucine-enkephalin, dynorphin A, dynorphin B, cholecystokinin, substance P, galanin and calcitonin gene-related peptide, was examined by immunohistochemistry in the human dorsal vagal complex including the nucleus of the solitary tract, the dorsal motor nucleus of the vagus and the area postrema. Immunoreactivity of all the twelve neuropeptides was found widely distributed in the various subdivisions of the nucleus of the solitary tract, showing a unique distribution for every peptide. Neuronal cell bodies immunostained with leucine-enkephalin, galanin and dynorphin B were found in this region. There were no immunopositive perikarya for any of the peptides in the other structures studied. Fibers containing galanin, corticotropin-releasing factor, substance P, dynorphin B, thyrotropin-releasing hormone and calcitonin gene-related peptide were observed at a relatively high density in the nucleus of the solitary tract. In the same structure, a moderately dense network of fibers immunostained with dynorphin A, cholecystokinin and leucine-enkephalin, but only solitary pro-opiomelanocortin-derived peptides-containing fiber fragments were observed. In the dorsal motor nucleus of the vagus the most prominent network of fibers was found to contain thyrotropin-releasing hormone, galanin and substance P. In contrast to these, no beta-endorphin immunoreactivity was detected. The area postrema contained only moderate to low densities of galanin-, substance P-, calcitonin gene-related peptide-, dynorphin B- and cholecystokinin-immunoreactive fibers.
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PMID:Neuropeptides in the human dorsal vagal complex: an immunohistochemical study. 784 71

The dorsal vagal complex contains many different neurotransmitter receptors. The cyto-architectural localizations of some of these receptors remain largely unknown. In rats, vagotomy was performed to destroy vagal afferents terminating in the nucleus of the solitary tract and to produce chromatolysis of preganglionic motoneurons in the dorsal motor nucleus of the vagus. Quantitative receptor autoradiography was then employed to determine the effect of vagotomy upon the distribution of receptors for thyrotropin-releasing hormone, substance P, and serotonin within individual regions and subnuclei of the entire dorsal vagal complex. Vagotomy reduced the concentrations of thyrotropin-releasing hormone and substance P, but not serotonin1A, or serotonin1B, receptors in the dorsal motor nucleus of the vagus. Within the nucleus of the solitary tract, substance P receptors were reduced in only the medial and central subnuclei after vagotomy. In contrast, no effect was observed upon the concentrations of thyrotropin-releasing hormone, serotonin1A, or serotonin1B receptors in any subnuclei of the solitary tract following vagotomy. These results suggest that in the dorsal motor nucleus of the vagus, thyrotropin-releasing hormone and substance P receptors are localized upon vagal preganglionic motoneurons, while serotonin1A and serotonin1B receptors are present upon interneurons or other neuronal elements. These results also suggest that thyrotropin-releasing hormone, substance P, serotonin1A, and serotonin1B receptors in the nucleus of the solitary tract are localized upon internuncial neurons in the nucleus of the solitary tract.
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PMID:Effects of vagotomy on neurotransmitter receptors in the rat dorsal vagal complex. 838 19


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