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)

The protective action of mild irritants has been established. However, the mechanisms as to how they antagonize the injurious action produced by the subsequent challenge with an ulcerogenic stimulus are still unclear. The present study examined the different protective mechanisms of an oral administration of the three mild irritants, 20% ethanol, 0.3 mol/L HCl or 5% NaCl against the gastric injurious actions of absolute ethanol in rats. In an attempt to clarify the pathways and mediators involved in the adaptive cytoprotection, [D-Pro2, D-Trp7,9]-substance P (substance P antagonist), Nw-nitro-L-arginine methyl ester (L-NAME), indomethacin, capsaicin, lidocaine, atropine or hexamethonium was given. The protective action of 20% ethanol but not the other two mild irritants, was antagonized by L-NAME, indomethacin and capsaicin, which are the inhibitors of nitric oxide (NO) and prostaglandins (PG) synthesis, and afferent sensory neuron blocker, respectively. Substance P antagonist, lidocaine or atropine given alone, prevented mucosal damage; however, only substance P antagonist enhanced the anti-lesion action of 20% ethanol, while atropine and lidocaine increased the protective effect of NaCl and HCl. The three mild irritants increased the residual gastric secretion. Only 20% ethanol and 5% NaCl but not 0.3% HCl significantly increased the basal adherent mucus and also attenuated the mucus depletion by absolute ethanol. It is concluded that the cytoprotective action of either ethanol or NaCl seems to be mediated through the increase of residual gastric secretion and adherent mucus. In the ethanol-treated group, these actions could act through the afferent sensory fibres, with NO and PG as the possible mediators.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The differential mechanisms of mild irritants on adaptive cytoprotection. 753 52

The frequency of spontaneous action potentials of locus coeruleus (LC) neurons was recorded extracellularly in pontine slices of the rat brain. Ethanol (1-100 mM) elevated the firing rate in most neurons; this effect was concentration-dependent. (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 0.03-1 microM), kainate (0.1-3 microM), N-methyl-D-aspartate (NMDA; 1-30 microM), substance P (0.01-1 microM), nicotine (0.1-10 microM) and alpha,beta-methylene ATP (alpha,beta-meATP; 0.3-30 microM), all increased the firing. Application of ethanol (10-100 mM) to the superfusion medium for 10 min, reproducibly and concentration-dependently inhibited the facilitatory effect of NMDA (10 microM). However, the inhibitory effect of ethanol (100 mM) decreased during a 30-min superfusion period and after the wash-out of ethanol the sensitivity of LC neurons to NMDA (10 microM) tended to overshoot above their initial level. Although NMDA was more potent in the absence than in the presence of external Mg2+, ethanol (100 mM) continued to depress the facilitatory effect of a low concentration of NMDA (3 microM) in a Mg(2+)-free medium. By contrast, in a medium containing normal Mg2+, ethanol (100 mM) failed to significantly interfere with the increase in firing rate induced by a high concentration of NMDA (30 microM). The effects of kainate (0.5 microM), AMPA (0.3 microM) and nicotine (1 microM) were also depressed by ethanol (100 mM), while the effects of substance P (0.03 microM) and alpha,beta-meATP (30 microM) were not changed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition by ethanol of excitatory amino acid receptors and nicotinic acetylcholine receptors at rat locus coeruleus neurons. 753 98

Methods for extraction and isolation of intact RNA are often laborious, time consuming, and preclude the direct analysis of peptides. Similarly, the conditions for extraction and isolation of peptides are unsuitable for the isolation of intact RNA. Thus, to study changes in the levels of neuropeptides and gene expression of the corresponding mRNAs, separate procedures are required. A simple and rapid method for the simultaneous extraction of RNA and peptides from tissues is described. RNA and peptides are extracted with guanidinium isothiocyanate, followed by delipidation, and peptides are isolated by a simple solid-phase extraction procedure. RNA is isolated by differentially partitioning DNA into an organic phase, followed by precipitation with ethanol. The RNA and peptides isolated by this method are of high yield and quality. Furthermore, this method for RNA isolation is successful and efficient, even with tissues that proved recalcitrant with other procedures, and allows the simultaneous processing of multiple samples. We describe the successful application of this procedure for measuring tachykinins and the corresponding preprotachykinin A mRNA from tissues. Extraction of neuropeptide K, a 36-mer tachykinin, was dramatically more efficient with the present method than other methods in common use.
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PMID:Simultaneous extraction of total RNA and peptides from tissues: application to tachykinins. 753 24

The selective NK3 tachykinin agonist senktide evokes in rodents 5-HT mediated behaviors, including 5-HT2 receptor-mediated wet dog shakes (WDS) and head shakes (HS). It was observed previously that genetically selected Sardinian alcohol-preferring (sP) rats show a small number of WDS and HS following intracerebroventricular (ICV) injection of senktide. The present study was aimed at confirming these observations and at providing information on the reasons accounting for the anomalous response of sP rats. Senktide (500-2000 ng/rat, ICV) produced a much lower number of WDS and HS in sP rats than in nonselected Wistar (nsW) rats. Both behaviors were suppressed by the 5-HT2 antagonist ritanserin (1 mg/kg, subcutaneously), confirming that 5-HT2 receptors mediate the response. HS induced by the ICV injection of 5-HT agonists endowed with marked activity at 5-HT2 receptors, such as quipazine (1500-6000 ng/rat) or DOI (500-3500 ng/rat), were much less pronounced in sP rats than in nsW rats. Moreover, WDS following peripheral injection of 5-hydroxytryptophan, 25-100 mg/kg, and carbidopa, 12.5 mg/kg, were less intense in sP and in ethanol-naive sP rats than in nsW and in Sardinian alcohol-nonpreferring rats. These findings suggest that sP rats have an inherent different regulation of central 5-HT2 mechanisms.
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PMID:Low responsiveness to agents evoking 5-HT2 receptor-mediated behaviors in Sardinian alcohol-preferring rats. 754 92

The present study evaluated the effect of SC injections of the selective NK3 tachykinin agonist, Suc-[Asp6,MePhe8]substance P(6-11), also referred to as senktide (SENK), on 8% alcohol intake in genetically selected alcohol-preferring rats. Animals were offered access to 8% ethanol for 2 h/day (between 1800 and 2000 h) and to tap water for 4 h/day (between 1800 and 2200 h); SENK was injected 10 min before access to fluids. The peptide significantly reduced alcohol intake at doses of 125 and 250 micrograms/kg, but not at 62.5 micrograms/kg. The reduction in alcohol intake was accompanied by a sharp increase in water intake, so that total fluid intake was never significantly modified. The same SC doses of SENK did not modify water intake in rats with access to water, as the only fluid, for 4 h/day. In food-deprived rats food intake was not altered by 125 micrograms/kg, whereas 250 micrograms/kg produced a reduction in food intake that was smaller in intensity and shorter lasting than the reduction in alcohol intake. The same doses of SENK did not modify 0.1% saccharin intake, nor did they elicit major competing behaviors. The results of the present study are in keeping with those obtained following central injection of NK3 agonists, and show that a behaviorally selective reduction of alcohol intake can be evoked also by peripheral administration of SENK.
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PMID:Subcutaneous injections of the tachykinin senktide reduce alcohol intake in alcohol-preferring rats. 754 65

The impact of ethanol on the male reproductive axis are multiple and varied, with both gonadal and control hypothalamic-pituitary pertubations being reported. There appears to be a discrepancy, however, between the in vivo and in vitro effects of ethanol on hypothalamic luteinizing hormones releasing hormone (LHRH) and the pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH). While in vivo data suggests a decrease in LHRH release after EtOH, in vitro studies find no effect on secretion. Similarly, in vivo acute EtOH profoundly diminishes LH synthesis and secretion, while in vitro impaired release with no alteration in the transcription of beta LH has been found. A potential exploration for these discrept results could be the in vivo metabolism of EtOH into acetaldehyde and acetate, or the subsequent formation of salsolinol, a product of acetate combining with dopamine. To test this possibility, a series of in vitro experiments were conducted exposing dispensed anterior pituitary cells from male rats to different doses of acetaldehyde, acetate or salsolinol for varying amounts of time for which gonadotropin secretion and beta LH mRNA levels were assessed. The results demonstrated no effect of either acetaldehyde or acetate on basal or LHRH stimulated LH release, FSH release or steady-state beta LH mRNA levels. These data suggest that the metabolites of EtOH, which occur in vivo but not in vitro, are not responsible for the discrepant gonadotropin changes reported between the in vivo and in vitro setting. Other potential mechanisms to explain this phenomenon include differences in the molarity of EtOH, hyperprolactinemia and suprapituitary influences including hypothalamic LHRH, catecholamines, excitatory amino acids, substance P and beta endorphin.
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PMID:Failure of ethanol metabolites to alter gonadotropin secretion or luteinizing hormone synthesis in vitro. 758 34

In the presence of substance P (SP; 10 microM), serotonin (5-HT; 1 microM) triggered a cation permeability in cells of the hybridoma (mouse neuroblastoma x rat glioma) clone NG 108-15 that could be assessed by measuring the cell capacity to accumulate [14C]guanidinium for 10-15 min at 37 degrees C. In addition to 5-HT (EC50 0.33 microM), the potent 5-HT3 receptor agonists 2-methyl-serotonin, phenylbiguanide, and m-chlorophenylbiguanide, and quipazine, markedly increased [14C]guanidinium uptake in NG 108-15 cells exposed to 10 microM SP. In contrast, 5-HT3 receptor antagonists prevented the effect of 5-HT. The correlation (r = 0.97) between the potencies of 16 different ligands to mimic or prevent the effects of 5-HT on [14C]guanidinium uptake, on the one hand, and to displace [3H]zacopride specifically bound to 5-HT3 receptors on NG 108-15 cells, on the other hand, clearly demonstrated that [14C]guanidinium uptake was directly controlled by 5-HT3 receptors. Various compounds such as inorganic cations (La3+, Mn2+, Ba2+, Ni2+, and Zn2+), D-tubocurarine, and memantine inhibited [14C]guanidinium uptake in NG 108-15 cells exposed to 5-HT and SP, as expected from their noncompetitive antagonistic properties at 5-HT3 receptors. However, ethanol (100 nM), which has been reported to potentiate the electrophysiological response to 5-HT3 receptor stimulation, prevented the effects of 5-HT plus SP on [14C]guanidinium uptake. The cooperative effect of SP on this 5-HT3-evoked response resulted neither from an interaction of the peptide with the 5-HT3 receptor binding site nor from a possible direct activation of G proteins in NG 108-15 cells. Among SP derivatives, [D-Pro9]SP, a compound inactive at the various neurokinin receptor classes, was the most potent to mimic the stimulatory effect of SP on [14C]guanidinium uptake in NG 108-15 cells exposed to 5-HT. Although the cellular mechanisms involved deserve further investigations, the 5-HT-evoked [14C]guanidinium uptake appears to be a rapid and reliable response for assessing the functional state of 5-HT3 receptors in NG 108-15 cells.
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PMID:Characteristics of [14C]guanidinium accumulation in NG 108-15 cells exposed to serotonin 5-HT3 receptor ligands and substance P. 768 66

To elucidate the possible role of vasoactive intestinal peptide (VIP) in the pathogenesis of acute gastric mucosal damage, rats were treated intragastrically with 1.0 ml 96% ethanol with or without intravenous or intraperitoneal coadministration of VIP (1 nmol/liter to 1 mumol/liter/100 g). VIP was found to double the mean lesion area when compared with that induced by ethanol alone (P < 0.05), an effect that was prevented by VIP antagonist (1 mumol/liter/100 g). A substance P antagonist (1 mumol/liter/100 g) also reduced the extent of gastric damage induced by coadministration of VIP and ethanol. VIP antagonist or substance P antagonist significantly reduced ethanol-induced gastric mucosal damage. Gastric mucosal levels of LTB4, LTC4, VIP, and substance P were significantly increased in ethanol-treated rats as compared with saline-treated animals (P < 0.05). The augmentation of ethanol-induced damage by VIP was associated with increased gastric mucosal levels of LTB4. In VIP-treated rats, gastric mucosal levels of substance P were found to be significantly increased compared with control rats (P < 0.05). Administration of VIP to pyloric-ligated rats significantly increased gastric acid output and blood pepsinogen A levels as compared with saline treated rats (P < 0.05). Ketotifen, a mast cell stabilizer (100 micrograms/100 g), administered orally 30 min before damage induction by ethanol, with or without VIP, totally abolished the damage of the surface epithelium of the entire gastric mucosa and significantly reduced the mucosal levels of LTC4 and LTB4 (P < 0.05). It is suggested that VIP is involved in the pathogenesis of acute ethanol-induced gastric mucosal damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of vasoactive intestinal peptide (VIP) in pathogenesis of ethanol-induced gastric mucosal damage in rats. 768 41

The effects of injection of substance P (SP) into the hypothalamic supraoptic vasopressinergic nucleus (SON) in water-loaded and ethanol-anesthetized rats were examined. Substance P and its analog [D-Pro2, D-Trp7,9]SP induced marked decreases in urine outflow, with a ED50 value of approx. 0.4 and 0.9 nmol, respectively. The antidiuresis of SP was inhibited by a prior injection of [D-Arg1, D-Trp7,9, Leu11]SP (spantide), an SP-receptor antagonist into the SON. After the injection of SP, urine osmotic pressure was increased by threefold, and the urine level of arginine-vasopressin (AVP) was elevated by 70-fold. The effects of SP and [D-Pro2, D-Trp7,9]SP were completely blocked by pretreatment with an intravenous injection of d(CH2)5-D-Tyr(Et)VAVP, an AVP (V1V2)-receptor antagonist. A prior injection of atropine, a muscarinic receptor antagonist, inhibited the effect of [D-Pro2, D-Trp7,9]SP, but not that of SP. The results suggest that SP, injected into the SON, causes antidiuresis through the release of AVP. A possible mechanism for the antidiureses induced by SP and [D-Pro2, D-Trp7,9]SP is discussed.
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PMID:Substance P injected into the hypothalamic supraoptic nucleus causes antidiuresis through the release of arginine-vasopressin in water-loaded and ethanol-anesthetized rats. 768 55

The tachykinin-1 gene in mammals produces structurally-related regulatory peptides, substance P (SP), neurokinin A (NKA), neuropeptide K (NPK) and neuropeptide-gamma. The production of these peptides is regulated by both differential mRNA transcription and post-translational precursor processing. Such processes are known to be highly tissue- and species-specific. In this study, we have examined tachykinin-1 gene expression and precursor processing in porcine ocular tissues by employing specific tachykinin radioimmunoassays coupled with reverse phase HPLC characterization. Optic nerve, cornea, iris, ciliary body, retina, choroid and sclera were micro-dissected from freshly enucleated porcine eyes (n = 10). Following acidified ethanol extraction of tissues, dried extracts were reconstituted and subjected to two radioimmunoassays, one of which is highly specific for intact SP, the other for NKA, NKB, NPK and neuropeptide-gamma. In all tissue extracts except the retina, the molar concentration of SP immunoreactivity was significantly greater than that of NKA. These data would imply expression of both alpha- and beta-preprotachykinin-1 in these ocular tissues. Reverse phase HPLC analysis confirmed the presence of authentic SP and NKA in all tissue extracts. However, in extracts of the retina, NKA immunoreactivity co-eluted with synthetic NPK standard. These chromatographic data suggest differential processing of the beta-preprotachykinin-1 precursor in the retina compared with the other ocular tissues. Thus differential mRNA transcription of the tachykinin-1 gene coupled with differential precursor processing appears to occur in porcine ocular tissues and may be a process of functional significance in the regulation of visual physiology.
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PMID:Tachykinin-1 gene products in porcine ocular tissues: evidence for transcriptional and post-translational regulation. 768 18


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