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)

Using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," one can identify and localize minute amounts of bioactive substances (including neurotransmitters), micro-organisms, toxic substances, or drugs, and, in addition, one can non-invasively image normal organs as well as screen for and image the distribution of specific types of cancer of specific internal organs without using any expensive instrumentation. One can also use this method to perform a qualitative analysis of neurotransmitters, neuromodulators, and hormones on different parts of the imaged organs. The molecule or substance being investigated is compared with a minute amount of a pure control reference substance, and if the substance identical to the control reference substance exists, then the electro-magnetic waves emitted by the identical substance will produce an electro-magnetic resonance phenomenon with the electro-magnetic waves of identical resonance frequency emitted by the control reference substance, and this resonance phenomenon is hypothesized to be the basis of the "Bi-Digital O-Ring Test Molecular Identification and Localization Method." The following substances have been used as control reference substances to identify and localize identical substances in vitro and in vivo: pure neurotransmitters (e.g. serotonin, beta-endorphin, methionine-enkephalin, norepinephrine, dopamine, L-dopa, substance P, etc.), as well as L-tryptophan and L-tyrosine; cholesterol; steroid hormones (including aldosterone, corticosterone, cortisol, progesterone, testosterone, etc.); peptide hormones; microscopic slides of normal organs; microscopic slides of specific cancer cells of specific organs (e.g. adenocarcinoma of the head of the pancreas, adenocarcinoma of the descending colon, etc.); microscopic slides of pure micro-organisms; toxic substances (e.g. lead, mercury, KCN); drugs (including non-steroidal anti-inflammatory drugs, antibiotics, beta-blockers, calcium channel blockers, etc.); and antibodies against specific substances or micro-organisms. An intensive network of serotonin and L-tryptophan was discovered, by using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," in different parts of the body. In general, in painful areas, frequently serotonin is markedly reduced, L-tryptophan is markedly increased, and substance P is markedly increased, while in non-painful areas, serotonin is markedly increased, L-tryptophan is markedly decreased, and substance P is markedly decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:"Bi-digital o-ring test molecular identification and localization method" and its application in imaging of internal organs and malignant tumors as well as identification and localization of neurotransmitters and micro-organisms--Part 1. 287 19

Picomolar concentrations of neurotensin caused concentration-dependent contractions of the longitudinal musculature of the fundus of the rat stomach. The EC50 of neurotensin was approximately 1.5 nM. On a molar basis neurotensin was about 5-10 times more potent than 5-hydroxytryptamine (5-HT) and approximately 80 times as active as acetylcholine in producing similar contractions. Studies with structurally related peptides indicated that whereas the carboxy terminal portion of neurotensin was essential for biological activity, a substantial part of its amino terminus end could be removed without affecting its potency. The EC50 for the neurotensin fragment 8-13 was identical to that of neurotensin, however its 1-8 or 1-11 fragments were completely inactive. Tetrodotoxin did not modify the potency of neurotensin or structurally related analogues suggesting that the neurotensin receptor is probably located on the smooth muscle membrane. In addition, the potency of neurotensin in contracting the fundus was not modified by pretreatment with atropine, methysergide or diphenhydramine. Fade to the contractile response of neurotensin was followed by the development of tachyphylaxis; desensitization was concentration-dependent and characterized by a shift in the agonist concentration-response curve to the right and downwards. Desensitization with a priming concentration of neurotensin (approx. EC50) caused a substantial blockade of its excitability. There was cross-desensitization between neurotensin and the contractile activity of neurotensin 8-13 or xenopsin, but not with angiotensin II, bradykinin, substance P, acetylcholine, 5-HT or histamine. Pretreatment of the fundus strip with verapamil 0.3-1 microM antagonized in a concentration-dependent fashion the neurotensin-induced contractions but not the muscular contractions caused by acetylcholine. It is concluded that neurotensin activates a specific excitatory receptor probably located on the cell membrane of the smooth muscles of the rat fundus. In addition, we suggest that this receptor is somehow related to a voltage-dependent calcium channel, sensitive to verapamil.
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PMID:Excitatory neurotensin receptors on the smooth muscle of the rat fundus: possible implications in gastric motility. 298 83

The aim of this study was to compare the stimulus-response characteristics of the cholinergic and tachykininergic excitatory transmission to the circular muscle of the guinea-pig proximal colon and their susceptibility to inhibition by the N-type calcium channel blocker omega-conotoxin (CTX). All experiments were performed in the presence of guanethidine (3 microM), indomethacin (10 microM), L-nitroarginine (L-NOARG, 30 microM) and apamin (0.1 microM). In the presence of the tachykinin receptor antagonists, FK 888 (10 microM0 and GR 94,800 (3 microM), to block NK1 and NK2 receptors, respectively, electrical field stimulation (EFS) produced frequency-dependent atropine- (1 microM) sensitive contractions. In the presence of atropine (1 microM), EFS produced tachykininergic contractions which were abolished by the combined administration of FK 888 (10 microM) and GR 94,800 (3 microM). The maximal responses produced by cholinergic and tachykininergic neurotransmission ranged between 80 and 100% of the maximal contractile response to 80 mM KCl. The frequency of stimulation, pulse width and voltage required to produce 50% of the maximal cholinergic and tachykininergic contraction were not different from each other, although cholinergic transmission appeared more efficient in producing twitch contractions in response to single pulse EFS. Furthermore, cholinergic transmission was more efficient than tachykininergic transmission in producing contraction in response to short periods of EFS. CTX (0.1 microM for 30 min) produced a large and comparable rightward shift of the cholinergic and tachykininergic frequency-response curve (19 and 17 fold increase in the frequency of stimulation producing 50% of the maximal response, respectively) and markedly depressed (51 and 43% inhibition, respectively) the maximal concentrations response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of omega-conotoxin on cholinergic and tachykininergic excitatory neurotransmission to the circular muscle of the guinea-pig colon. 753 90

It has recently been shown that two novel tachykinins, ranakinin and [Leu3, Ile7]neurokinin A, are present in fibers innervating the frog adrenal gland, and it has been demonstrated that tachykinins stimulate corticosteroid secretion in vitro through activation of chromaffin cells. The purpose of the present study was to investigate the effect of ranakinin on cytosolic free calcium concentrations ([Ca2+]i) and to determine the source of calcium involved. Cultured adrenal cells were loaded with the fluorescent calcium indicator indo-1, and changes in [Ca2+]i were studied using dual emission wavelength microfluorimetry. Administration of a brief pulse of ranakinin (1 microM; 1 sec) in the vicinity of chromaffin cells caused an immediate and transient increase in [Ca2+]i. Repeated pulses of ranakinin resulted in a gradual decline in the [Ca2+]i response, suggesting the occurrence of a desensitization phenomenon. Preincubation of the cells with the calcium channel blockers nifedipine (10 microM) and omega-conotoxin (1 microM) did not alter the response of chromaffin cells to ranakinin. Chelation of extracellular calcium by EGTA (10 mM) caused a marked decrease in the basal [Ca2+]i, but did not suppress the ranakinin-induced [Ca2+]i increase. Conversely, incubation of the cells with thapsigargin (10 microM), an inhibitor of calcium adenosine triphosphatase activity, abolished the stimulatory effect of ranakinin, indicating that the increase in [Ca2+]i can be ascribed to mobilization of calcium from intracellular stores. Preincubation of adrenal cells with the phospholipase C antagonist U-73122 (1 microM; 18 min) or with pertussis toxin (10 microM; 18 h) totally blocked the ranakinin-induced [Ca2+]i rise. Taken together, these data indicate that in frog adrenochromaffin cells, ranakinin causes mobilization of calcium from intracellular stores. The effect of ranakinin is mediated through activation of a phospholipase C via a pertussis toxin-sensitive G protein.
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PMID:Effect of ranakinin, a novel tachykinin, on cytosolic free calcium in frog adrenochromaffin cells. 766 74

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

Opioid agonists induced an increase in the intracellular free calcium concentration ([Ca2+]i) or an inhibition of K+ (25 mM)-stimulated increase in [Ca2+]i in different subsets of mouse dorsal root ganglion (DRG) neurons. The total neuronal population was grouped into three classes according to somatic diameter and defined as small ( < 16 microns), intermediate (16-25 microns), or large ( > 25 microns) neurons. Substance P-like immunoreactivity was detected mainly in the small and intermediate neurons. The delta, kappa, and mu opioid receptor agonists [D-Ser2,Leu5]enkephalin-Thr (DSLET), U69593, and [D-Ala2, MePhe4, Glyol5]enkephalin (DAMGO) each induced a transient increase in [Ca2+]i in a small fraction ( < 30%) of neurons. The increases in [Ca2+]i were blocked by the opioid antagonist naloxone. The dihydropyridine-sensitive calcium channel blocker nifedipine also blocked the increase in [Ca2+]i induced by 1 microM DSLET. The rank order of potency (percentage of cells responding to each opioid agonist) was DSLET > U69593 > DAMGO. The opioid-induced increase in [Ca2+]i was observed mainly in large neurons, with a low incidence in small and intermediate neurons. Opioid agonists also caused inhibition of K(+)-stimulated increases in [Ca2+]i, which were blocked by naloxone (1 microM). Inhibition of the K(+)-stimulated increase by 1 microM DSLET or U69593 was greater in small and intermediate neurons than in large neurons.
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PMID:Opioid regulation of intracellular free calcium in cultured mouse dorsal root ganglion neurons. 873 52

Changes in the background impulse activity of midbrain central gray substance neurons have been studied on slice preparations from the rat midbrain upon application of calcium-free solution, an activator of calcium channels, BAY-K 8644 (10 nM), organic (verapamil, 40 microM; D600, 10 microM; nifedipine, 1-10 microM; amiloride, 1 microM) and inorganic (Co2+, 1.5 mM) calcium channel blockers. Besides BAY-K 8644, all the substances inhibited most of the neurons studied. Verapamil, BAY-K 8644 and Co2+ also revealed facilitatory effects. Facilitatory action of BAY-K was most effective in silent neurons and in those previously inhibited by amiloride. Latent period values of inhibition in calcium-free solution and upon application of organic and inorganic blockers have the following sequence: D600 > amiloride > verapamil > Co2+ > nifedipine > calcium-free solution. Maximum rise time had the following order: amiloride > D600 > nifedipine > verapamil > Co2+ > calcium-free solution. Complete suppression of the neuronal activity induced by amiloride lasted twice as long as that induced by calcium-free solution, Co2+ and nifedipine, and six times as long as verapamil-induced suppression. Preliminary application of calcium channel blockers reduced facilitatory and increased inhibitory effects of serotonin and substance P. Data obtained are discussed with the supposition in mind that inhibition of the function of calcium channels in central gray substance neurons could be one of the mechanisms underlying the analgesic effect of a series of neurotropic agents after their introduction into this structure.
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PMID:Modulation of the activity of midbrain central gray substance neurons by calcium channel agonists and antagonists in vitro. 884 21

Tachykinins are present in the anterior pituitary gland and there is evidence that they may have a direct intrapituitary role influencing the secretion of some of the hormones released by this gland. In this investigation, we have studied the effect of the non-peptide NK-2 receptor antagonist SR 48,968 (Sanofi Recherche) on the basal release of LH, FSH, and prolactin by rat hemipituitaries incubated in vitro, and also on the response to GnRH. SR 48,968 significantly inhibited prolactin release into the medium. The highest doses of this compound stimulated the basal release of LH by hemipituitaries from castrated, castrated testosterone-treated, and ovariectomized estradiol-treated rats, but not from intact male rats. SR 48,968 significantly inhibited the release of LH in response to GnRH. Since some tachykinin receptor antagonists have been demonstrated to act also on calcium channels, studies with verapamil, a calcium channel antagonist, were also carried out for comparison. Verapamil inhibited prolactin release into the medium and decreased the LH response to GnRH. These results suggest that tachykinins that bind NK-2 receptors, may have an intrapituitary role stimulating the release of prolactin, and that they may also modulate the response of the gonadotrophs to GnRH. The fact that verapamil shares some of the actions exerted by NK-2 receptor antagonists on the pituitary glandm however, suggests the possibility that some of the effects of NK-2 receptor antagonists may be mediated through calcium channel antagonism. Therefore, the results observed with the use of some of these antagonists should be interpreted with great caution.
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PMID:Effect of a non-peptide NK-2 tachykinin receptor antagonist on LH, FSH, and prolactin release by rat hemipituitaries in vitro. 937 29

Migraine is a common and disabling disease of uncertain pathogenesis. Research on the trigeminovascular system, serotonin receptors, and substance P have provided clues to improving the pharmacotherapy of this disorder. Selective serotonin agonists, such as sumatriptan, dihydroergotamine, ergotamine tartrate, nonsteroidal anti-inflammatory drugs (NSAIDS), isometheptene mucate, and phenothiazines are useful to treat acute attacks. Prophylactic agents include beta-blockers, calcium channel blockers, NSAIDs, antidepressants, and valproate. The addition of several new agents for the acute and prophylactic therapy of migraine has improved the outlook for this debilitating disorder.
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PMID:The pharmacology of medications used in treating headache. 942 44

We investigated the effects of KB-2796 (1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride), a novel calcium channel blocker, on neurogenic inflammation caused by electrical stimulation in the trigeminal ganglion and on cutaneous reactions induced by inflammatory mediators in rats, by measuring plasma extravasation. Neurogenic inflammation was inhibited by pretreatment with capsaicin (25 mg/kg, s.c.) but not indomethacin (10 mg/kg, i.p.), while phosphoramidon (2.5 mg/kg, i.v.) augmented it. KB-2796 (0.1-1 mg/kg, i.v.) significantly inhibited neurogenic inflammation in a dose dependent manner, without affecting histamine-, bradykinin- or substance P-induced cutaneous reactions. Dimetotiazine (0.3 and 1 mg/kg, i.v.), flunarizine (1 mg/kg, i.v.), mepyramine (1 mg/kg, i.v.) and sumatriptan (1 mg/kg, i.v.) significantly inhibited neurogenic inflammation. However, these compounds also showed complete or partial inhibition of histamine-, bradykinin- or substance P-induced reactions. Nifedipine (0.1 mg/kg, i.v.) did not show marked effects on neurogenic inflammation and cutaneous reactions. The present experiments indicate that neurogenic inflammation is presumably mediated not only by neuropeptides released from trigeminal nerve endings but also by secondarily released histamine, and that KB-2796 like sumatriptan may inhibit neurogenic inflammation caused by trigeminal nerve stimulation probably through inhibition of neuropeptide release but its inhibition may be distinct from the calcium blocking action of the 1,4-dihydropyridine type.
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PMID:Effects of KB-2796 on plasma extravasation following antidromic trigeminal stimulation in the rat. 950 71

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