UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We produced thiamine deficiency by treating mice with a thiamine deficient (TD) diet, but not with pyrithiamine, a thiamine antagonist. Twenty days after TD feeding, a significant antinociceptive effect was observed in the formalin test. A single injection of thiamine HCl (50 mg/kg, s.c.) on the 19th day after TD feeding (on the late TD stage) failed to reverse the antinociceptive effect, the muricide effect, and impairment of avoidance learning induced by TD feeding, as compared to pair-fed controls. These results indicate the possibility that the TD-induced antinociceptive effect may result from irreversible changes in the spinal and/or brain neurons. To clarify the involvement of substance P (SP) and somatostatin (SST) systems in the spinal cord, we examined the effect of intrathecal (i.t.) injections of these agonists on TD feeding-inducd elevation of pain threshold. I.t. injection of SP and SST elicited a behavioral response consisting of reciprocal hindlimb scratching, biting and/or licking of hindpaws. There was no significant difference in the behavioral response to SP between TD mice and PF mice on the 5th day after feeding. However, on the 10th and 20th day after TD feeding the response to SP was significantly increased compared with PF mice. This phenomenon was also observed with SST on the 20th day after TD feeding. These results indicate the possibility that TD feeding may produce an increased behavioral response to SP and SST through an enhanced sensitivity of neurokinin-1 and SST receptors in the spinal cord. Taken together, the antinociceptive effect following TD feeding may result from a decrease in spinal SP and SST contents.
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PMID:Antinociceptive effect following dietary-induced thiamine deficiency in mice: involvement of substance P and somatostatin. 1150 48

Intestinal mucosal capsaicin-sensitive afferent nerves mediate, in part, the protective mesenteric hyperemia after intraduodenal acidification. Mechanisms associated the sensory neuropeptides, e.g. calcitonin gene-related peptide (CGRP), substance P, and ruthenium red-sensitive cation channels contribute to acid-induced mesenteric hyperemia, but whether they play a role in protection against acid-induced duodenal villous damage is not known. We tested the hypothesis that in doses that attenuate acid-induced hyperemia, inhibitors of these mechanisms will exacerbate acid-induced duodenal villous damage. Intravenous vehicle, specific receptor antagonists of CGRP (CGRP(8-37)), substance P (CP 96345), intraduodenal ruthenium red or vehicle was administered, followed by intraduodenal perfusion with 0.1 N HCl. Duodenal tissue was processed for hematoxylin and eosin staining. Villous damage was scored by blinded observers. Deep villous injury was significantly increased after treatment with ruthenium red, but not with CGRP(8-37) or CP 96345. These findings support the hypothesis that ruthenium red-sensitive cation channels, but not neuropeptides associated with intestinal mucosal afferent nerves, are involved in the acid-sensing mechanism which mediates the protection against acid-induced duodenal villous damage.
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PMID:Ruthenium red-sensitive cation channels, but not calcitonin gene-related peptide or substance P-mediated mechanisms, protect duodenal villi against acid-induced damage. 1235 80

10.1152/jn.00224.2002. Dopamine (DA) modulates the cardiorespiratory reflex by peripheral and central mechanisms. The aim of this study was to examine the role of DA in synaptic transmission of the nucleus tractus solitarius (NTS), the major integration site for cardiopulmonary reflexes. To examine DA's role, we used whole cell, voltage-clamp recordings in a rat horizontal brain stem slice. Solitary tract stimulation evoked excitatory postsynaptic currents (EPSCs) that were reduced to 70 +/- 5% of control by DA (100 microM). The reduction in EPSCs by DA was accompanied by a decrease in the paired pulse depression ratio with little or no change in input resistance or EPSC decay, suggesting a presynaptic mechanism. The D1-like agonist SKF 38393 Br (30 microM) did not alter EPSC amplitude, whereas the D2-like agonist, quinpirole HCl (30 microM), depressed EPSCs to 73 +/- 4% of control. The D2-like receptor antagonist, sulpiride (20 microM), abolished DA modulation of EPSCs. Most importantly, sulpiride alone increased EPSCs to 131 +/- 10% of control, suggesting a tonic D2-like modulation of synaptic transmission in the NTS. Examination of spontaneous EPSCs revealed DA reversibly decreased the frequency of events from 9.4 +/- 2.2 to 6.2 +/- 1.4 Hz. Sulpiride, however, did not alter spontaneous events. Immunohistochemistry of NTS slices demonstrated that D2 receptors colocalized with synaptophysin and substance P, confirming a presynaptic distribution. D2 receptors also localized to cultured petrosal neurons, the soma of presynaptic afferent fibers. In the petrosal neurons, D2 was found in cells that were TH-immunopositive, suggesting they were chemoreceptor afferent fibers. These results demonstrate that DA tonically modulates synaptic activity between afferent sensory fibers and secondary relay neurons in the NTS via a presynaptic D2-like mechanism.
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PMID:Dopamine modulates synaptic transmission in the nucleus of the solitary tract. 1242 8

Gastroesophageal acid reflux (GER) is a common disorder associated with the exacerbation of asthma. In this study we investigated the effects on the airways of intraoesophageal HCl instillation in the rabbit and the role of tachykinins in these effects. In anaesthetized New Zealand rabbits bronchopulmonary functions [total lung resistance (R(L)) and dynamic compliance (C(dyn))] were calculated before and after HCl intraoesophageal instillation. Infusion of HCl induced a significant bronchoconstriction (P < 0.05) in the terms of R(L) and C(dyn) changes, that were increased by phosphoramidon pre-treatment and reduced by capsaicin pre-treatment. Moreover, a pre-treatment with SR 48968, a tachykinin NK2 receptor antagonist, or SR 140333, a NK1 receptor antagonist, significantly inhibited the bronchoconstriction induced by intraoesophageal HCl infusion in terms of R(L) and C(dyn)changes. Finally, the HCl induced bronchoconstriction was unaffected by SR 142801, a tachykinin NK3 receptor antagonist. In conclusion these results suggest that bronchoconstriction induced by intraoesophageal HCl infusion is mainly dependent on the release of tachykinins and that both NK1 and NK2 tachykinin receptors are involved.
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PMID:Role of tachykinins in the bronchoconstriction induced by HCl intraesophageal instillation in the rabbit. 1250 44

Challenge of the rat gastric mucosa with 0.5 mol L(-1) HCl activates nitrergic neurons in the myenteric plexus as visualized by c-Fos immunohistochemistry. In the present study, we characterized the activated neurons more extensively by their chemical coding and investigated whether a neural pathway that involves capsaicin-sensitive extrinsic afferents and/or cholinergic neurons transmitting via nicotinic receptors contributes to the activation of myenteric neurons. In multiple labelling experiments, c-Fos was examined for co-localization with nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), enkephalin (ENK), gastrin-releasing peptide (GRP), substance P (SP), calbindin D-28k (CALB) and neurofilament 145 (NF 145). All c-Fos-positive neurons were immunoreactive for NOS, VIP, NPY and NF 145, but not for SP, ENK, GRP and CALB. Nerve fibres co-expressing NOS, VIP and NPY were predominantly found in the external muscle layer and in the muscularis mucosae but rarely in the mucosa. Pre-treatment with capsaicin or hexamethonium or a combination of both pre-treatments reduced HCl-induced c-Fos expression by 54, 66 and 63%, respectively. Acid challenge of the stomach, therefore, leads to activation of presumably inhibitory motor neurons responsible for muscle relaxation. Activation of these neurons is partly mediated by capsaicin-sensitive afferents and involves ganglionic transmission via nicotinic receptors.
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PMID:Capsaicin-sensitive extrinsic afferents are involved in acid-induced activation of distinct myenteric neurons in the rat stomach. 1258 67

Whole cell patch-clamp techniques were used to examine neurokinin receptor modulation of Ca2+ channels in small to medium size dorsal root ganglia neurons (<40 pF) that express mainly N- and L-type Ca2+ currents. Low concentrations of substance P enhanced Ca2+ currents (5-40%, <0.2 microM), while higher concentrations applied cumulatively reversed these enhancements (5-28% reductions, >0.5 microM). This apparent inhibition by high concentrations of substance P was blocked by the administration of the NK3 antagonist SB 235,375 (0.2 microM). The NK1 agonist, [Sar9,Met11]-substance P (0.05 to 1.0 microM) did not alter Ca2+ currents; whereas the NK2 agonist, [betaAla8]-neurokinin A (4-10), enhanced Ca2+ currents (5-36% increase, 0.05-0.5 microM). The enhancement was reversed by the NK2 antagonist MEN 10,376 (0.2 microM) but unaffected by the NK3 antagonist SB 235,375 (0.2 microM). The NK3 agonist [MePhe7]-neurokinin B (0.5-1.0 microM) inhibited Ca2+ currents (6-24% decrease). This inhibition was not prevented by the NK2 antagonist MEN 10,376 (0.2 microM) but was blocked by the NK3 antagonist SB 235,375 (0.2 microM). Both the enhancement and inhibition of Ca2+ currents by neurokinin agonists were reversed by the protein kinase C inhibitor bisindolylmaleimide I HCl (0.2-0.5 microM). Following inhibition of Ca2+ channels by [MePhe7]-neurokinin the facilitatory effect of BayK 8644 (5 microM) was increased and the inhibitory effect of the N-type Ca2+ channel blocker w -conotoxin GVIA (1 microM) was diminished, suggesting that the NK3 agonist inhibits N-type Ca2+ channels. Similarly, block of all but N-type Ca2+ channels, revealed that [betaAla8]-neurokinin A (4-10) enhanced the currents while [MePhe7]-neurokinin B inhibited the currents. Inhibition of all but L-type Ca2+ channels, revealed that [betaAla8]-neurokinin A (4-10) enhanced the currents while [MePhe7]-neurokinin B had no effect. Activation of protein kinase C with low concentrations of phorbol-12,13-dibutyrate enhanced Ca2+ currents, but high concentrations inhibited N- and L-type Ca2+ currents. In summary, these data suggest that in adult rat dorsal root ganglia neurons, NK2 receptors enhance both L- and N-type Ca2+ channels and NK3 receptors inhibit N-type Ca2+ channels and that these effects are mediated by protein kinase C phosphorylation of Ca2+ channels.
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PMID:Protein kinase C is involved in neurokinin receptor modulation of N- and L-type Ca2+ channels in DRG neurons of the adult rat. 1266 Mar 48

The neuropeptide leptin has been shown to selectively modulate rat chorda tympani (CT) responses to sweet tastants. To explore whether other neuropeptides can modulate such responses, rat whole nerve CT responses to NaCl, HCl, quinine HCl, and sucrose were measured while administering cholecystokinin-8 (CCK-8), substance P(4-11) (SP(4-11)), or calcitonin gene-related peptide (CGRP). To avoid possible confounding effects on CT responses that take long times to develop, such as those that arise from intraperitoneal injections, we investigated the effects of the above peptides injected into the ipsilateral lingual artery (LA) on CT nerve responses during the initial seconds after a tastant was placed on the tongue. We found that CT responses to NaCl and HCl were increased by CCK-8 and decreased by CGRP. SP(4-11) had no noticeable effect. Peptide-induced CT responses to quinine HCl or sucrose were too small to accurately detect. These data suggest that at short latencies, after local infusion via the LA, neuropeptides can alter CT responses in a peptide-specific manner.
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PMID:Neuropeptides modulate rat chorda tympani responses. 1273 81

Previously, we reported that the injection of capsaicin into the lateral cerebroventricle (i.c.v.) stimulated gastric acid secretion via vanilloid VR1 receptors and the vagal cholinergic pathways in anesthetized rats. In the present study, we investigated the involvement of receptor systems for neurokinin A, calcitonin gene-related peptide (CGRP) and glutamate in the vanilloid VR1 receptor-mediated response. The i.c.v. injection of neurokinin A (30 nmol) stimulated gastric acid secretion in the presence of cis-2-(diphenylmethyl)-N-[(2-iodophenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine oxalate (L-703606, a tachykinin NK1 receptor antagonist, 30 nmol) and the effect was inhibited by cyclo[Gln-Trp-Phe-Gly-Leu-Met] (L-659877, a tachykinin NK2 receptor antagonist, 30 nmol); the values were 145.9 +/- 32.3 and 21.1 +/- 16.6 microEq HCl per 120 min, respectively. The value in the control group was 14.3 +/- 3.8 microEq HCl. The tachykinin NK2 receptor-mediated secretion was inhibited by i.c.v. injections of antagonists of the CGRP1 receptor (human CGRP fragment 8-37, 15 nmol) and non-N-methyl-D-aspartate (non-NMDA)-type glutamate receptor (6-cyano-7-nitroquinoxaline-2,3-dione, 10.9 nmol); the values were 30.8+/-29.8 and 5.7+/-16.9 microEq HCl, respectively. Gastric acid secretion induced by the i.c.v. injection of 30 nmol capsaicin (178.4 +/- 34.0 microEq HCl) was inhibited by antagonists of tachykinin NK2 (23.7 +/- 6.2) and CGRP1 (21.2 +/- 8.5), but not tachykinin NK1 (181.4 +/- 37.0), receptors. The gastric acid secretion induced by capsaicin was decreased by the i.c.v. pre-injection of low doses of neurokinin A or CGRP, which alone had no effect on the secretion. These findings suggest the involvement of tachykinin NK2, CGRP and non-NMDA receptor systems in the vanilloid VR1 receptor-mediated regulation of gastric acid secretion in the rat brain regions close to the lateral cerebroventricle.
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PMID:Role of neuropeptide receptor systems in vanilloid VR1 receptor-mediated gastric acid secretion in rat brain. 1498 54

Little is known about transmitters that encode noxious gastric stimuli in the spinal cord. The release of glutamate, substance P, and CGRP from the spinal cord was therefore investigated in response to acid injury of the gastric mucosa. Dorsal halves of the caudal thoracic spinal cord (T7-T13) were removed 6 h after oral application of 0.5 M HCl or saline, transferred to a superfusion chamber, and the basal and capsaicin-stimulated (3.3 microM) transmitter release was determined. After acid injury, basal glutamate release increased 134% as compared to saline-treated animals. Capsaicin-stimulated release of CGRP and SP was 48% and 58% lower in acid- than in saline-treated animals, indicating that capsaicin-sensitive fibers in the dorsal spinal cord were already partially depleted by acid treatment. Capsaicin denervation reduced basal glutamate release by 33% after acid injury as compared to non-denervated acid-treated animals. Gastric origin and capsaicin sensitivity of glutamatergic, CGRP- and SP-containing primary afferents in thoracic dorsal root ganglia were then determined by retrograde tracing with True Blue and immunohistochemical labeling with the vanilloid receptor TRPV1. About 65% of True Blue-labeled cells were glutamatergic and more than 73% of this population expressed the TRPV1 receptor. Nearly all True Blue/CGRP (85%)- and True Blue/SP-positive cells (97%) coexpressed TRPV1. We conclude that noxious gastric stimulation with acid induces release of glutamate, SP, and CGRP from capsaicin-sensitive sensory afferents in the dorsal horn of the spinal cord where they may play an important role in gastric nociception and hyperalgesia.
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PMID:Nociceptive transmitter release in the dorsal spinal cord by capsaicin-sensitive fibers after noxious gastric stimulation. 1578 Oct 52

We studied the anatomical properties of parasympathetic postganglionic neurons in the frog tongue and their modulatory effects on taste cell responses. Most of the parasympathetic ganglion cell bodies in the tongue were found in extremely small nerve bundles running near the fungiform papillae, which originate from the lingual branches of the glossopharyngeal (GP) nerve. The density of parasympathetic postganglionic neurons in the tongue was 8000-11,000/mm(3) of the extremely small nerve bundle. The mean major axis of parasympathetic ganglion cell bodies was 21 microm, and the mean length of parasympathetic postganglionic neurons was 1.45 mm. Electrical stimulation at 30 Hz of either the GP nerve or the papillary nerve produced slow hyperpolarizing potentials (HPs) in taste cells. After nicotinic acetyl choline receptors on the parasympathetic ganglion cells in the tongue had been blocked by intravenous (i.v.) injection of D-tubocurarine (1 mg/kg), stimulation of the GP nerve did not induce any slow HPs in taste cells but that of the papillary nerve did. A further i.v. injection of a substance P NK-1 antagonist, L-703,606, blocked the slow HPs induced by the papillary nerve stimulation. This suggests that the parasympathetic postganglionic efferent fibers innervate taste cells and are related to a generation of the slow HPs and that substance P is released from the parasympathetic postganglionic axon terminals. When the resting membrane potential of a taste cell was hyperpolarized by a prolonged slow HP, the gustatory receptor potentials for NaCl and sugar stimuli were enhanced in amplitude, but those for quinine-HCl and acetic acid stimuli remained unchanged. It is concluded that frog taste cell responses are modulated by activities of parasympathetic postganglionic efferent fibers innervating these cells.
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PMID:Taste cell responses in the frog are modulated by parasympathetic efferent nerve fibers. 1624 66

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