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)

Whether the influx of calcium through voltage-operated channels is involved in the stimulatory effects of substance P and neurokinin A in airways smooth muscle is not yet firmly established. This question was addressed in the present study using guinea pig trachea and human bronchi suspended in normal or calcium-free Krebs solution and tested with inhibitors of calcium channels. In calcium-free Krebs solution, the myotropic effects of substance P (10(-7) M), neurokinin A (3.10(-8) M), acetylcholine (2.10(-5) M), and histamine (2.10(-5) M) were reduced by 27-57%, while those of potassium chloride and tetraethylammonium were practically abolished. Calcium antagonists such as verapamil or nicardipine, when applied at concentrations of 10(-8)-10(-6) M, inhibited the contractions produced by potassium chloride and tetraethylammonium, whereas higher concentrations (10(-5)-10(-4) M) of both inhibitors were needed to reduce the effects of substance P, neurokinin A, acetylcholine, and histamine. In neither preparation did the calcium agonist Bay K 8644 (10(-6) M) modify the effects of neurokinin A, substance P, acetylcholine, or histamine, but it potentiated potassium chloride's effect on human bronchi. We conclude that transmembrane calcium influx through voltage-operated channels plays a minor role in the stimulatory effects of neurokinins in airways smooth muscle.
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PMID:Role of extracellular calcium in the effects of substance P and neurokinin A on guinea pig trachea and human bronchus. 245 27

The aim of the present study was to establish an experimental model, previously used in cat, for studying tachykinin release from the rat spinal cord in vivo and to compare the results with those obtained in vitro. Stimulation with pulses of 40 mM potassium or 10 microM capsaicin in the spinal cord superfusion fluid increased the release of substance P (SP)- and neurokinin A (NKA)-like immunoreactivity (LI) both in vivo and in vitro. The amounts of SP-LI and NKA-LI released by potassium in vitro were 1.02 +/- 0.12 and 1.17 +/- 0.22 fmol/mg tissue, respectively. Also the ratio between the amounts released by two consecutive potassium stimulations were similar for SP-LI and NKA-LI. Reversed-phase high performance liquid chromatography of the NKA-LI released in vitro by potassium or capsaicin revealed a major immunoreactive component coeluting with synthetic NKA. Despite the use of highly sensitive radioimmunoassays, basal release of SP-LI and NKA-LI was found only in 9 of 31 in vivo experiments. In these, peripheral electrical stimulation of the sciatic nerves (50 Hz, 50 V and 0.05 ms or 10 Hz, 10 V and 5 ms) induced an increase of the SP-LI and NKA-LI levels in the superfusates. This increase persisted for more than 40 min after a 2 min stimulation. In most experiments, however, no SP-LI or NKA-LI could be detected in the superfusates, neither at basal conditions nor following electrical nerve stimulation. Similarly, no release of SP-LI could be detected in response to various noxious mechanical, thermal or chemical stimuli applied to the skin. The present results demonstrate that the superfused rat spinal cord may be used to study in vivo release of tachykinins in response to intense chemical stimulation of the entire spinal cord. However, the method seems to be less suitable for studies of tachykinin release in response to electrical activation engaging only a few spinal segments or in response to natural noxious stimuli. The results obtained in vitro suggest that SP and NKA are released in equimolar amounts from the spinal cord upon stimulation with potassium.
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PMID:Tachykinin release from rat spinal cord in vitro and in vivo in response to various stimuli. 245 22

Static muscular contraction has been shown to increase cardiovascular and ventilatory function in reflex manner. The sensory arm of this reflex arc is comprised of group III and IV muscle afferents. The discharge properties of these muscle afferents whose activation causes the pressor reflex response to contraction were investigated. Group III afferents were more responsive to mechanical stimuli, such as tendon stretch and probing their receptive fields than were group IV afferents. In contrast, group III afferents were less responsive to ischemic contraction than were group IV afferents. Equal percentages of group III and IV afferents were stimulated by potassium, lactic acid and arachidonic acid, each of which are metabolic products of contraction. Adenosine, phosphate and lactate, however, had no effect on the discharge of the afferents. Intrathecal injection of antagonists or antibodies to substance P and somatostatin attenuated the pressor response to contraction by about half, a finding that suggests a role for these 2 peptides in the spinal transmission of the reflex.
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PMID:Pressor reflex response to static muscular contraction: its afferent arm and possible neurotransmitters. 245 28

Recent evidence suggests that activation of airway C-fibers, besides causing afferent transmission, also causes release of transmitters from peripheral endings, probably via local axon reflexes, resulting in effects on vascular and bronchial smooth muscle, i.e., vasodilatation, increase in vascular permeability, and bronchoconstriction. In the present study, the release of tachykinins was investigated in the perfused guinea pig lung by various ways of neuronal activation. Substance-P-like immunoreactivity (SP-LI) and neurokinin-A-like immunoreactivity (NKA-LI) was determined by radioimmunoassay in the perfusates. A significantly increased outflow of both SP-LI and NKA-LI was observed during perfusion of the lung with high potassium concentration (60 mM), the C-fiber activator capsaicin (1 microM), bradykinin (1 microM), histamine (100 microM), or the nicotinic agonist dimethylphenyl piperazinium (DMPP) (32 microM). Release of both SP-LI and NKA-LI could also be achieved by electrical stimulation of vagal nerves. The percental increase varied from 80 to 1,000% depending on the kind of stimulus. The release of tachykinins by K+ or capsaicin was greatly reduced in calcium-free medium. Release by histamine was completely inhibited by 1 microM mepyramine, and release by DMPP was abolished by 20 microM hexamethonium. High performance liquid chromatography indicated that NKA-LI consisted of several cross-reacting substances, presumably other peptides of the tachykinin family. Among the isolated mammalian tachykinins, NKA was the most potent one to contract tracheal smooth muscle of guinea pigs in vitro, followed by neurokinin B and by SP. Both NKA and SP relaxed the guinea pig pulmonary artery with similar potency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenyl piperazinium, and vagal nerve stimulation. 246 73

The effect of extracellular calcium on the release of calcitonin gene-related peptide (CGRP) induced by electrical field stimulation from enteric nerves of isolated rat ileum was studied; the effect of high potassium, veratridine and caffeine was also examined. Release of endogenous substance P from enteric nerves was also measured for comparison. Electrical field stimulation (10 Hz, 0.3 ms for 2 min) of the ileum preparation caused a significant (P less than 0.001) increase in the release of CGRP and substance P from enteric nerves. The evoked, but not the basal, release of both CGRP and substance P was inhibited in the presence of tetrodotoxin (TTX). The release of CGRP and substance P induced by electrical stimulation was abolished in Ca2+-free medium containing CDTA and also in normal medium containing the calcium channel blocker cadmium chloride (CdCl2), with no change in the level of the basal release of both peptides. However, potassium depolarization (76 and 110 mM) failed to evoke an increase in the release of endogenous CGRP, although it did cause an increase in the release can be induced by mobilization of calcium from intracellular Ca2+ stores. Veratridine, on the other hand, did not cause an increase in CGRP release, although substance P and VIP release was induced by veratridine from the same preparations. The results of the present study have demonstrated that CGRP release from enteric nerves requires the presence of extracellular calcium but, unlike substance P and most other transmitters reported to show calcium-dependent release, potassium depolarization does not induce CGRP release from enteric nerves of rat ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of calcitonin gene-related peptide from rat enteric nerves is Ca2+-dependent but is not induced by K+ depolarization. 246 7

The relationship between receptor-mediated increases in the intracellular free calcium concentration [( Ca]i) and the stimulation of ion fluxes involved in fluid secretion was examined in the rat parotid acinar cell. Agonist-induced increases in [Ca]i caused the rapid net loss of up to 50-60% of the total content of intracellular chloride (Cli) and potassium (Ki), which is consistent with the activation of calcium-sensitive chloride and potassium channels. These ion movements were accompanied by a 25% reduction in the intracellular volume. The relative magnitudes of the losses of Ki and the net potassium fluxes promoted by carbachol (a muscarinic agonist), phenylephrine (an alpha-adrenergic agonist), and substance P were very similar to their characteristic effects on elevating [Ca]i. Carbachol stimulated the loss of Ki through multiple efflux pathways, including the large-conductance Ca-activated K channel. Carbachol and substance P increased the levels of intracellular sodium (Nai) to more than 2.5 times the normal level by stimulating the net uptake of sodium through multiple pathways; Na-K-2Cl cotransport accounted for greater than 50% of the influx, and approximately 20% was via Na-H exchange, which led to a net alkalinization of the cells. Ionomycin stimulated similar fluxes through these two pathways, but also promoted sodium influx through an additional pathway which was nearly equivalent in magnitude to the combined uptake through the other two pathways. The carbachol-induced increase in Nai and decrease in Ki stimulated the activity of the sodium pump, measured by the ouabain-sensitive rate of oxygen consumption, to nearly maximal levels. In the absence of extracellular calcium or in cells loaded with the calcium chelator BAPTA (bis[o-aminophenoxy]ethane-N,N,N',N'-tetraacetic acid) the magnitudes of agonist- or ionomycin-stimulated ion fluxes were greatly reduced. The parotid cells displayed a marked desensitization to substance P; within 10 min the elevation of [Ca]i and alterations in Ki, Nai, and cell volume spontaneously returned to near baseline levels. In addition to quantitating the activation of various ion flux pathways in the rat parotid acinar cell, these results demonstrate that the activation of ion transport systems responsible for fluid secretion in this tissue is closely linked to the elevation of [Ca]i.
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PMID:Effects of muscarinic, alpha-adrenergic, and substance P agonists and ionomycin on ion transport mechanisms in the rat parotid acinar cell. The dependence of ion transport on intracellular calcium. 246 62

Substance P (SP) is found in high concentration in the nucleus tractus solitarius (NTS), and is a neurotransmitter candidate in primary baroreceptor afferents to the NTS. Release of SP in the medial NTS of halothane-anesthetized rabbits was measured by in vivo microdialysis. Bilateral electrical stimulation of the aortic depressor nerves (ADN) elicited a significant elevation in SP collected during the period following stimulation, while sham stimulation had no effect. Perfusion through the dialysis probe with a high-potassium (150 mM) solution caused a large increase in the level of SP collected, verifying the neural origin of this release. Possible explanations for the delay in increased release of SP include interaction with carotid afferents, diffusion time, or excitation of SP-containing inputs to the NTS originating elsewhere in the brain. This study demonstrates that SP release in the NTS is elevated by activation of baroreceptor afferents, supporting the hypothesis that SP plays a role in the central integration of cardiovascular control. Whether this release is from primary afferent terminals, or from another source, remains to be seen.
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PMID:Release of substance P in the nucleus tractus solitarius measured by in vivo microdialysis: response to stimulation of the aortic depressor nerves in rabbit. 246 13

Brain tissue levels and in vivo release of substance P (SP) and neurokinin A (NKA) and GABA were measured bilaterally in striatum and substantia nigra of the rat, after a unilateral 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway. Sham injected animals served as controls. The dopamine denervation decreased the tissue levels of SP in striatum (-38%) ipsilateral to the lesion and in substantia nigra both ipsi- (-54%) and contralateral (-38%) to the lesion. NKA was not significantly changed in the striatum, but decreased (like SP) in the substantia nigra both ipsi- (-50%) and contralateral (-40%) to the lesion. GABA tissue levels increased in the denervated striatum (+20%) and remained unchanged in substantia nigra at both sides. The extracellular levels of SP, NKA and GABA were measured with microdialysis in vivo at basal conditions and during stimulation with potassium administered locally via the microdialysis probe. The stimulated release of SP and NKA in the substantia nigra ipsilateral to the lesion was compared to in sham operated animals reduced with 39% and 64%, respectively, while no change in SP or NKA release was detected in the striatum. The basal release of GABA in the striatum was increased with 296% and with 76% during stimulation in the dopamine denervated striatum, while no change in GABA basal or stimulated release was detected in the substantia nigra. We suggest that the increased GABA release in the dopamine denervated striatum may be due to a decreased dopamine mediated inhibition of local GABA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue levels and in vivo release of tachykinins and GABA in striatum and substantia nigra of rat brain after unilateral striatal dopamine denervation. 246 14

Microdialysis combined with sensitive radioimmunoassays was used to measure the in vivo release of substance P (SP) and neurokinin A (NKA) in the rat substantia nigra. The effect of acute and subchronic haloperidol treatment (0.5 mg/kg) on the basal and potassium-evoked release was studied. No significant effect was observed after a single injection. However, pretreatment with haloperidol for 10 days decreased the potassium-induced release of SP and NKA by 25 and 27%, respectively. The basal overflow of NKA was reduced by 29%, while no significant effect could be seen on the basal release of SP.
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PMID:Subchronic haloperidol treatment decreases the in vivo release of tachykinins in rat substantia nigra. 247 May 96

Incubation of rat peritoneal mast cells with substance P resulted in the transient stimulation of phosphoinositol breakdown and histamine secretion through an exocytotic process. These effects were inhibited markedly by a prior 2-hr exposure of the cells to pertussis toxin. Pertussis toxin also inhibited exocytosis induced by substance P, mastoparan and compound 48/80, but did not modify the secretory effect of the ionophore A23187. The transfer of rat peritoneal mast cells from balanced salt solution to calcium-free buffer led to a similar time-dependent decrease in their response to substance P and mastoparan. The concomitant absence of potassium from the calcium-free buffer enabled the mast cells to retain their secretory response. These data demonstrate identical dependency for calcium and monovalent ions of the secretory process elicited by substance P, mastoparan and compound 48/80. Pretreatment of mast cells with neuraminidase decreased the secretagogic effect of substance P, mastoparan and compound 48/80 without modifying the efficiency of the ionophore A23187. Thus, sialic acid residues might be involved in the initial binding of peptides and compound 48/80 to mast cells, which activate a pertussis toxin-sensitive G-protein and allows the increase in phospholipase C activity to induce exocytosis. This sequence of events might characterize the physiological pathway of mast cell activation by peptides, without necessarily requiring selective membrane receptors.
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PMID:Activation of rat peritoneal mast cells by substance P and mastoparan. 247 89


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