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)

Idiopathic vulvodynia is vulvar discomfort in which a diagnosis has not yet been established. As in other idiopathic pain syndromes, the involvement of primary afferent fibers (PAFs) has been postulated as playing a role in the pathogenesis and maintenance of idiopathic vulvodynia. Capsaicin induces the release of substance P (SP) by PAFs, producing vasodilation and increasing vascular permeability (neurogenic inflammation). Likewise, it has been shown that acid solutions can stimulate PAFs with the release of SP. To evaluate the pain threshold in women with idiopathic vulvodynia, 10 patients with vulvar pain but without significant vulvar physical changes and 10 asymptomatic controls received topically applied acetic acid solutions with increasing hydrogenionic concentrations (pH 3, 2.5, 2, 1.5, 1.2). Results related to pain threshold and pain time monitoring and intensity were analyzed with Fisher's exact and Wilcoxon's tests, respectively. Our data suggest that in idiopathic vulvodynia the pain threshold for acid solutions is decreased, probably in relation to increased sensitivity of PAFs involved in the transduction of painful signals.
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PMID:Idiopathic vulvodynia. Clinical evaluation of the pain threshold with acetic acid solutions. 760 71

The effect of taurine on nociception was investigated in adult male Swiss mice using the formalin and acetic acid tests. Taurine (50-200 mg/kg) injected sc into the animals (N = 6 per group) 30 min before formalin injection into the right hind paw reduced formalin-induced early phase (0-5 min) licking activity by 30-42%, but had no effect on the late phase (20-25 min) response. Writhing responses induced by acetic acid injected ip were also significantly inhibited by 49% and 56% by doses of 100 and 200 mg/kg taurine, respectively. In both tests taurine demonstrated antinociception which was significantly blocked by naloxone (1 mg/kg, sc, administered simultaneously with taurine). The naloxone-sensitive antinociceptive action of taurine was probably mediated via modulation of endogenous pain-regulatory systems that involve opioid peptides, neuropeptides like substance P and amino acids such as glutamate and aspartate.
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PMID:Taurine modulates chemical nociception in mice. 813 33

1. Release of substance P in the dorsal horn is considered a primary event in the perception of pain. The profile of racemic RP67580, a non-peptide antagonist at the NK1 (substance P) receptor, was examined in a range of antinociception tests on rodents. 2. At doses up to 30 mg kg-1, s.c. racemic RP67580 exhibited antinociceptive activity in writhing and formalin paw tests in mice and gerbils. Acetic acid induced writhing and the licking response to formalin were reduced to 40-50% of the level observed in vehicle-treated animals (P < 0.05). However, this agent was not active in mouse tail flick, rat paw pressure or rat and guinea-pig formalin paw tests. 3. Like racemic RP67580, the calcium channel blockers nifedipine (30 mg kg-1, i.p.) and verapamil (10 or 20 mg kg-1, s.c.) inhibited the response to formalin by approximately 60% in gerbils (P < 0.05 compared with vehicle-treated animals). 4. Evidence for calcium channel antagonist activity of RP67580 was obtained in vitro. Racemic RP67580 inhibited calcium entry into depolarized strips of guinea-pig ileum longitudinal muscle myenteric plexus (apparent KB = 587 +/- 115 nM), inhibited [3H]-diltiazem binding to rabbit skeletal membranes (IC50 = 298 nM) and depressed high threshold calcium currents in neurones cultured from rat cortex (10% inhibition at 10 microM). 5. These findings indicate that the acute antinociceptive effects of RP67580 may not be attributable to a specific interaction with NK1 receptors and may be mediated via calcium channel blockade.
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PMID:Antinociceptive activity of NK1 receptor antagonists: non-specific effects of racemic RP67580. 830 8

The objective of this study was to document, through comprehensive means, normal distribution and concentration of catecholamines in various regions of the CNS of pigs, an increasingly popular animal model used for transgenic manipulation of neural genes. The effects of gonadal steroidal status on this distribution were also assessed by comparing CNS catecholamine concentrations among mature male pigs (boars), immature (gilts) and mature female pigs (sows), and adult male pigs castrated prepuberally (barrows). Dissected tissue samples from the CNS were extracted in 2 N acetic acid, filtered through a 0.2 micron filter, then quantitated by reverse-phase high performance liquid chromatography using a C-18 reverse phase column with electrochemical detection. In both boars and sows the highest concentrations of norepinephrine (NE) were found in the diencephalic areas and brain stem. Gilts exhibited elevated concentrations of NE in the olfactory bulbs (OB), hypothalamus, pons, and corpus trapezoideum-locus ceruleus (LC) compared to lower concentrations in corresponding areas of sows. Prepuberal castration of the male was associated with significantly lower NE concentrations in the striatum, periaqueductal area (PAG), pons, LC, and spinal cord. The sow exhibited significantly lower NE concentrations in the mammillary area (Mam), PAG, pons, and spinal cord than those in corresponding areas of the boar. Dopamine concentrations appeared to be similar in all areas of the brain and spinal cord studied in the sow and boar. Results demonstrated that prepuberal castration of the male appears to significantly alter the DA content of the Mam and dorsal spinal cord, in contrast to gilts who possess significantly higher concentrations of DA. It is concluded from our studies that in general, catecholamine concentrations in various regions of the brain and spinal cord of sexually mature pigs parallel distributions of neuropeptides, substance P, and methionine enkephalin, as previously reported. In addition, significant association was found between gonadal activity and catecholamine concentrations in discrete areas of the pig brain.
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PMID:Distribution of catecholamines in the central nervous system of the pig. 837 8

We developed a method for measuring neuropeptides and monoamines in the same rat brain tissue and applied this method to study the effects of electroconvulsive stimuli (ECS) on these compounds. Rats were treated with repeated ECS or sham ECS. After sacrifice by focused microwave irradiation, brains were dissected and immediately frozen. The tissues were extracted in acetic acid. After lyophilization the samples were reconstituted in phosphate buffer and divided in three fractions: (1) was further purified on a cation-exchange column before catecholamines were measured on a high-performance liquid chromatography (HPLC) system, (2) for measuring serotonin on the HPLC system, (3) for measuring peptide concentrations by specific radioimmunoassays. Confirming our previous findings, ECS significantly increased neuropeptide Y-like immunoreactivity (-LI) in hippocampus and frontal cortex and neurokinin A-LI in the hippocampus, while no changes in substance P- and neurotensin-LI were detected. New findings were a decrease in noradrenaline concentrations in the frontal and occipital cortex and hippocampus, an increase in dopamine concentrations in the frontal and occipital cortex and no serotonin change. In summary, we have developed methods to measure both peptides and monoamines in the same brain tissue specimens, and have shown that ECS leads to changes in both neuropeptides and classical neurotransmitters in distinct brain regions.
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PMID:Concurrent analysis of neuropeptides and biogenic amines in brain tissue of rats treated with electroconvulsive stimuli. 858 1

We examined the effect of KW-4679 ((Z)-11-[(3-dimethylamino) propylidene]-6,11-dihydro-dibenz[b,e]oxepin-2-acetic acid monohydrochloride), an anti-allergic drug, on the tachykinin-mediated airway response in guinea pigs. Electrical stimulation of the vagus nerve in atropine-treated and propranolol-treated guinea pigs caused a 38.1% decrease in dynamic compliance (Cdyn), which was suppressed by the combination of the tachykinin NK1-receptor antagonist (+/-)-CP-96345 and NK2-receptor antagonist SR 48968. KW-4679 at a dose of 3 mg/kg significantly reduced the decrease in Cdyn (P < 0.05). On the other hand, KW-4679 did not inhibit substance P or neurokinin A-induced decrease in Cdyn. These results suggest that KW-4679 may inhibit the tachykininergic airway response by prejunctional inhibition of peripheral sensory nerves.
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PMID:Inhibitory effect of KW-4679, an anti-allergic drug, on tachykinin-mediated airway response induced by electrical vagal stimulation in guinea pigs. 883 45

The role of platelet-activating factor (PAF) and substance P in stimulating abnormal motor activity during ileal inflammation was investigated in conscious dogs. All test substances were infused close-i.a. in short segments of the ileum. Ileal inflammation was induced by mucosal exposure to a series of ethanol and acetic acid infusions. In the normal state, PAF stimulated phasic contractions and some giant migrating contractions (GMCs), whereas substance P stimulated only phasic contractions. During inflammation, PAF stimulated a significantly greater number of GMCs, but there was no significant difference in the area under phasic contractions between the normal and inflamed states. Atropine, tetrodotoxin, hexamethonium, verapamil, diltiazem, and dantrolene significantly inhibited the response to PAF in both the normal and the inflamed state. By contrast, inhibition of nitric oxide by N omega-nitro-L-arginine methyl ester enhanced the contractile response to PAF. N-(6-ammohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride, a calmodulin antagonist, did not affect the response to PAF. Methacholine, neostigmine and motilin stimulated only phasic contractions during the normal state, but they stimulated both phasic contractions and GMCs during the inflamed state. We conclude that PAF is one of the inflammatory response mediators that may stimulate GMCs during ileal inflammation. The inflammatory response may modulate the enteric neuronal and cellular control of contractions such that the cholinergic mechanisms of stimulation of GMCs are sensitized during inflammation.
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PMID:Platelet-activating factor (PAF) stimulates giant migrating contractions during ileal inflammation. 885 95

1. The antinociceptive action of clonidine (Clon) and the interactions with alpha 1, alpha 2 adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test). 2. Clon produced a dose-dependent antinociceptive action and the ED50 for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg-1 vs 300 ng kg-1). The parallelism of the dose-response curves indicates activation of a common receptor subtype. 3. Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon-induced activity. These results suggest that alpha 1- and alpha 2-adrenoceptors, either located at the pre- and/or post-synaptic level, are involved in the control of spinal antinociception. 4. Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (microgram kg-1 range) and a lower antinociceptive effect at higher doses (mg kg-1 range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential mu opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P. 5. The results obtained in the present work suggest the involvement of alpha 1-, alpha 2-adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level.
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PMID:alpha-Adrenoceptor and opioid receptor modulation of clonidine-induced antinociception. 889 77

Polygala cyparissias (Polygalaceae) grows abundantly on Brazil's Atlantic coast, belonging to the typical underbrush vegetation of dunes and have been used in folk medicine for treatment of several diseases, such as disturbances of bowel and kidney. The hydroalcoholic extract of P. cyparissias (HE, 3 to 60 mg kg(-1), i.p. or 25 to 200 mg kg(-1), p.o.) produced significant and graded inhibition of acetic acid-induced abdominal constrictions, with mean ID50 values of 6 and 72 mg kg(-1), respectively. The HE (at this same range of doses) also produced dose-related inhibition of both the early and the late phase of formalin-induced licking. The calculated mean ID50 values for the early phase were: >60 and >200 mg kg(-1), while for the late phase they were 11 and 101 mg kg(-1), respectively, by i.p. and p.o. routes. The HE also caused dose-related inhibition of formalin-induced edema formation (P<0.01). The HE (3 to 60 mg kg(-1), i.p. or 50 to 200 mg kg(-1), p.o.) produced significant and dose-related inhibition of the neurogenic nociception caused by topical injection of capsaicin, with mean ID50 values of 12 and 71 mg kg(-1), respectively. Given orally, the HE (50 to 200 mg kg(-1)) prevented in a dose-dependent manner, bradykinin (3 nmol/paw) and substance P (10 nmol/paw)-induced hyperalgesia in the rat paw, with mean ED50 values of 122 and 121 mg kg(-1), respectively, but was ineffective in the hot-plate model of nociception. The antinociception caused by the HE, in contrast to that of morphine (5 mg kg(-1), s.c.), was not reversed by naloxone (5 mg kg(-1), i.p.) when assessed in the acetic acid writhing test. The HE, at antinociceptive doses, did not affect motor coordination of animals when assessed in the rota-rod model. The xanthone isolated from P. cyparissias, identified as 1,7-dihydroxy-2,3-dimethoxy xanthone (0.3 to 30 mg kg(-1), i.p.), produced dose-related inhibition of acetic acid-induced abdominal constriction, with mean ID50 value of 1.5 mg kg(-1). These data show that the active principle(s) present in the HE of P. cyparissias, elicited pronounced antinociception when assessed by i.p. or p.o. routes, against both inflammatory and neurogenic nociception, and was able to prevent bradykinin and substance P-induced hyperalgesia. Its precise mechanism of action still remains unclear.
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PMID:Antinociceptive properties of the hydroalcoholic extract and preliminary study of a xanthone isolated from Polygala cyparissias (Polygalaceae). 935 71

Inflammation suppresses phasic contractile activity in vivo. We investigated whether inflammation also suppresses in vitro phasic contractile activity and, if so, whether this could in part be due to the alteration of specific slow wave characteristics and morphology of the interstitial cells of Cajal (ICC). Circular muscle strips were obtained from normal and inflamed distal canine colon. Inflammation was induced by mucosal exposure to ethanol and acetic acid. The amplitudes of spontaneous, methacholine-induced, substance P-induced, and electrical field stimulation-induced contractions were smaller in inflamed muscle strips than in normal muscle strips. Inflammation reduced the resting membrane potential and the amplitude and duration of slow waves in circular muscle cells. Inflammation did not affect the amplitude of inhibitory junction potentials but did decrease their duration. Ultrastructural studies showed expansion of the extracellular space between circular muscle cells, reduction in the density of ICC and associated neural structures, damage to ICC processes, vacuolization of their cytoplasm, and blebbings of the plasma membrane. We conclude that inflammation-induced alterations of slow wave characteristics contribute to the suppression of phasic contractions. These alterations may, in part, be due to the damage to ICC. Inflammation impairs both the myogenic and neural regulation of phasic contractions.
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PMID:Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal. 943 48


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