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)

Substance P, given intrathecally at the second (T2) or ninth (T9) thoracic level in the anesthetized rat, increased heart rate, arterial pressure and circulating catecholamines. At T9 in adrenalectomized animals and at T2 in intact animals, the cardioacceleration was more abrupt than in intact animals injected at T9 suggesting that the adrenals are not necessary for the cardiovascular responses and that the adrenals may have released a factor which slows the neurally mediated cardioacceleration. As opioids are co-released with catecholamines from the adrenals, naloxone (10 mg/kg i.v.) or nalorphine HCl (which does not cross the blood-brain barrier; 10 mg/kg s.c.) was given 5 min before administration of substance P at T9 in intact rats. In both groups the cardioacceleration was similar to that elicited in adrenalectomized animals, indicating that the adrenal factor was opioid and that its action was peripheral rather than central. When propranolol (10 mg/kg i.v.) was given 3 or 15 min before, substance P increased arterial pressure but heart rate was unchanged, indicating that the opioid factor was not slowing the cardioacceleration by a direct effect on the heart. The results indicate that intrathecal administration of substance P produces a neurally mediated increase in arterial pressure and heart rate and induces the release of an adrenal opioid factor which slows the neurally-mediated cardioacceleration by an action in the periphery. This indicates a functional interaction between humoral and neural sympathetic mechanisms regulating the cardiovascular system.
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PMID:Neural mediation of the cardiovascular responses to intrathecal administration of substance P in the rat: slowing of the cardioacceleration by an adrenal opioid factor. 751 Mar 72

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

Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic construction of guinea-pig tracheal smooth muscle. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on constriction induced by the non-immunological mast cell degranulator-compound 48/80. Phosphoramidon produced significant leftward shift of the compound 48/80 concentration-response curve with corresponding decrease in the EC50 value from 51 (28-80) micrograms/ml to 42 (20-72) micrograms/ml. When added during the compound 48/80-induced constriction, phosphoramidon significantly increased the magnitude of this constriction by 69.7% after 30 min, and 78.9% after 45 min. Phosphoramidon was ineffective in tracheal rings from tachykinin-depleted guinea pigs. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl, 10 microM) and leukotriene receptor antagonist (ICI 198.615, 5 microM) significantly diminished the contractile response to compound 48/80 and prevented a phosphoramidon-dependent increase of this constriction. These results suggest that compound 48/80 induces the release of tachykinins by the stimulatory activity of histamine and leukotrienes. Anaphylactic release of tachykinins would therefore not depend directly on the antigen-antibody reaction.
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PMID:Inhibition of neutral endopeptidase potentiates compound 48/80-induced constriction of guinea-pig tracheal smooth muscle. 754 50

Ninety-five percent of the neurons in the corpus striatum of the rat are medium spiny projection neurons, which contain tachykinins such as substance P, neurokinin A, and neurokinin B and the opiate peptides, enkephalin and dynorphin. The remaining 5% consist of interneurons, of which a small but significant proportion are cholinergic. The influence of these cholinergic interneurons on the neuropeptidergic projection systems in the striatum is poorly understood at this time. The present study explores the relationship between cholinergic receptor activation or muscarinic blockade on striatal neuropeptide gene expression. Adult male Sprague-Dawley rats were treated chronically either with a cholinergic agonist (physostigmine: 0.5 mg/kg/3 x day), a muscarinic antagonist (scopolamine HCl: 0.4 mg/kg/3 x day), or vehicle (PBS: 0.1 ml/100 g) administered for 6 days (s.c.). In situ hybridization was performed with probes directed against mRNAs for beta-preprotachykinin (a transcript containing substance P, neurokinin A, and other tachykinins), neurokinin B and preproenkephalin. Physostigmine administration resulted in a 12% decrease in the dorsolateral caudate-putamen and a 27% increase in the core of the nucleus accumbens in substance P/neurokinin A mRNA; and a 29% increase in the caudate-putamen and an 11% increase in the core of the nucleus accumbens in preproenkephalin mRNA levels. Scopolamine treatment resulted in a 28% and 48% decrease, respectively, in the caudate-putamen and in the shell of the nucleus accumbens in substance P/neurokinin A mRNA levels. Neurokinin B mRNA levels were increased by 50% in the shell of the accumbens after scopolamine. Preproenkephalin mRNA levels increased by 24% in the caudate-putamen and decreased by 20% in the core of the nucleus accumbens. From these results we tentatively conclude that cholinoceptive neuropeptidergic neurons are segregated along dorsoventral and mediolateral axes in the striatum, thus giving rise to non-homogenous responses upon cholinergic receptor activation or muscarinic blockade.
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PMID:Cholinergic regulation of tachykinin- and enkephalin-gene expression in the rat striatum. 763 70

Using an isolated loop of the proximal duodenum of conscious rats, the role of vasoactive intestinal peptide (VIP) in the duodenal HCO3- response to HCl was examined, especially interactions with participating cholinoceptor mechanisms and prostaglandins. A 5-min perfusion with 150 mmol/liter HCl increased luminal VIP during 3 hr, with a peak output during and immediately after the acid challenge. The HCl-stimulated output was unaffected by atropine and hexamethonium, but was augmented by indomethacin from 13.6 (9.5-17.8) to 39 (20-85) fmol/cm/min. The HCO3- secretion in response to graded doses of intravenous VIP (0.00625-6 nmol/kg/30 min) was dose-dependent to maximally 33.5 +/- 10.5 mumol/cm/hr. The HCO3- secretion during a single intravenous infusion of VIP (12 nmol/kg/hr), 13.9 +/- 4.2 mumol/cm/hr, was unchanged by atropine, reduced to 10.0 +/- 3.5 mumol/cm/hr by hexamethonium, and augmented to 18.9 +/- 4.7 mumol/cm/hr by indomethacin. Exogenous VIP did not change the basal luminal output of PGE2; neither did exogenous PGE2 nor indomethacin affect the basal luminal output of VIP. HCl-induced increases in luminal outputs of VIP, substance P, and neurokinin A (the two latter with unknown roles) were differentially affected by atropine, hexamethonium, and indomethacin, indicating that the acid challenge released the peptides through controlled mechanisms. In conclusion, in the duodenal HCO3- response to luminal HCl, VIP may have a stimulatory role, which partially depends on nicotinic, but not on muscarinic cholinoceptor mechanisms, and which is negatively modulated by prostaglandins.
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PMID:HCl-stimulated duodenal HCO3- secretion in conscious rat. Interactions among VIP, nicotinic receptor mechanisms, and prostaglandins. 792 32

Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic contraction of guinea pig tracheal smooth muscle. Anaphylactic release of tachykinin-like substances was indicated. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on contraction induced by mediators of anaphylaxis. Phosphoramidon significantly increased histamine- and leukotriene D4-induced contractions of tracheal rings from unsensitized animals (by 14 and 48%, respectively), but failed to alter the contractile responses to prostaglandins D2 and F2 alpha. In tracheal rings preincubated with tachykinin antagonist-[D-Pro4, D-Trp7,9]-substance P(4-11), or in capsaicin-desensitized tracheal rings, phosphoramidon did not change histamine- and leukotriene D4-induced contractions. In the second part of the study, performed on tracheal rings obtained from ovalbumin-sensitized guinea pigs, we examined the effects of phosphoramidon on contractile responses to histamine and leukotrienes which are released after antigen challenge. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl) or leukotriene receptor antagonist (ICI 198.615) prevented a phosphoramidon-dependent increase of antigen-induced contraction. These results indicate that histamine and leukotrienes may be involved in the anaphylactic release of tachykinin-like substances or other neutral endopeptidase substratum.
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PMID:Phosphoramidon augments contraction of guinea pig tracheal smooth muscle induced by histamine and leukotriene-D4. 811 Dec 47

Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic contraction of guinea pig tracheal smooth muscle. It was suggested that anaphylactic release of tachykinin-like substances is likely to be responsible for the observed increases in tracheal contractions. To obtain additional information on the mechanisms responsible for anaphylactic release of tachykinins in guinea pig trachea, we examined the effects of phosphoramidon, an inhibitor of neutral endopeptidase, on contractile response to antigen after preincubation with the selective 5-lipoxygenase inhibitor AA-861. AA-861 (5 microM) significantly reduced ovalbumin-induced contraction, although the effect was not constant. A marked spontaneous increase in contraction was observed. Phosphoramidon (10 microM) produced significant increase of this contraction (27% after 30 min, and 33% after 45 min). The addition of H1-histamine receptor antagonist (diphenhydramine HCl, 10 microM) produced additional inhibition of the initial phase of antigen-induced contraction, while its later phase, apart from a spontaneous increment in magnitude, remained similar. Phosphoramidon (10 microM) increased the contraction by 26% after 30 min, and by 34% after 45 min. Since the effects of histamine and 5-lipoxygenase pathway products were prevented, we hypothesize that cyclooxygenase pathway products are responsible for the phosphoramidon-dependent increase in antigen-induced contraction. In accordance with previously reported ineffectiveness of contractile prostaglandins, we suggest that the relaxant prostaglandins are most important in mediating the release of tachykinins during the immediate hypersensitivity reaction in guinea pig trachea.
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PMID:Phosphoramidon modulates effects of the 5-lipoxygenase inhibition on anaphylactic contraction of the guinea pig trachea. 811 Dec 48

A new enzyme immunometric assay of small haptens containing primary amino groups (thyroxine, MW 777; substance P, MW 1347; endothelin, MW 2492) is described. The procedure involves different sequential steps: (1) immunocapture of the haptens (standard or sample) by monoclonal anti-hapten antibodies coated on 96-well microtiter plates; (2) cross-linking of haptens via their amino groups to the wells using homobifunctional reagents (glutaraldehyde or disuccinimidyl suberate); (3) denaturing treatments (HCl or methanol); (4) measurement of linked epitope using the same monoclonal anti-hapten antibodies labeled with acetylcholinesterase. A minimal detectable concentration in the 4-10 fmoL/mL range was observed. Each assay appeared to be 70-200 times more sensitive than conventional competitive enzyme immunoassay using the same monoclonal antibody-coated plate technology and acetylcholinesterase-hapten conjugates as enzymatic tracers. Precision and specificity were very satisfying. Good correlation was noted between this assay and the competitive assays performed for different biological samples (plasma, tissues, or supernatant cell culture).
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PMID:Immunometric assay of low molecular weight haptens containing primary amino groups. 811 75

During 30 days of thiamine deficiency (TD) feeding, the rat antinociceptive effect (pain threshold) to noxious heat stimulation was significantly increased in proportion to the decrease substance P (SP) fluorescent intensity in the spinal cord. Only a single injection of thiamine HCl (0.5 mg/kg, s.c.) on the early treatment day during TD feeding effectively reversed the analgesic effect to the pair-fed control level. Whereas this reversal effect by thiamine treatment was not found if this treatment was done on the relatively late day. However, either treatment day, except muricide, complete disappearance of various animal behaviours induced by TD was found. These results indicate that, after certain degree of TD development, TD-induced behavioral effects might be reversible, but the afferent nerve fibers might be irreversibly damaged, probably by the similar mechanism as found for an excitotoxin(s) mediated injury in the certain brain region(s). The results also suggest a possibility that SP and an excitotoxin, glutamate, in the dorsal part of the spinal cord greatly contribute to the pain transmission induced by noxious heat stimulation.
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PMID:Immunohistochemical determination of rat spinal cord substance P, and antinociceptive effect during development of thiamine deficiency. 857 71

The occurrence of inflammation as indicated by extravasation of Evans blue bound to plasma proteins was examined in various parts of the gastrointestinal tract in the rat, following administration of tachykinins, capsaicin and hydrochloric acid. Intravenous neurokinin A dose-dependently induced extravasation in stomach, duodenum, jejunum, caecum and colon, but had no effect in ileum. Neurokinin B equipotently induced extravasation in the stomach but had no effect in other parts of the gut and substance P had no effects on extravasation of Evans blue in any of the examined parts of the gastrointestinal tract. Capsaicin given intraperitoneally increased vascular permeability in stomach and duodenum only, while extravasation of Evans blue after capsaicin given intraluminally did not differ from the effect of the vehicle alone. As a comparison, HCl given intraluminally in the duodenum was found to induce a prominent extravasation of Evans blue of a greater magnitude than than of tachykinins. We suggest that tachykinins, and in particular neurokinin A, may be of importance for extravasation of plasma proteins as part of inflammatory reactions in the upper and lower gastrointestinal tract.
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PMID:Tachykinins increase vascular permeability in the gastrointestinal tract of the rat. 873 55


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