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 involvement of the histamine H3 receptor in the regulation of substance P release in neurogenic inflammation was studied by using rat hindpaw skin. R-(-)-alpha-Methylhistamine, a specific histamine H3 receptor agonist, significantly inhibited the increased vascular permeability induced by antidromic electrical stimulation of the sciatic nerve in a dose-dependent manner at doses of 0.5-3 mg/kg (i.v.), and thioperamide (2 mg/kg i.p.), a specific histamine H3 receptor antagonist, prevented the inhibitory effect of R-(-)-alpha-methylhistamine. The antidromic stimulation also caused a significant increase in immunoreactive substance P release in the subcutaneous (s.c.) perfusate in the rat hindpaw. R-(-)-alpha-Methylhistamine (0.25-2 mg/kg) dose dependently inhibited the increase in release of immunoreactive substance P, and thioperamide (2 mg/mg i.p.) antagonized it. Perfusion of histamine (10(-3) M) elicited a significant increase of immunoreactive substance P release in the perfusate, which was reduced by R-(-)-alpha-methylhistamine and the antagonism of thioperamide was also observed. Histamine (in the presence of histamine H1 and H2 receptor antagonists) had an inhibitory effect on the electrically evoked release of immunoreactive substance P. These results strongly support the hypothesis that histamine regulates substance P release via prejunctional histamine H3 receptors that are located on peripheral endings of sensory nerves.
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PMID:Regulation of substance P release mediated via prejunctional histamine H3 receptors. 753 82

Substance P elicits histamine release from human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma, we examined the ability of substance P to stimulate human mast cells obtained at bronchoalveolar lavage (BAL). BAL samples were obtained at routine bronchoscopy from 35 non-preselected patients. Histamine release experiments were performed in a standard manner using substance P and the calcium ionophore A23187. Both substance P (50 microM) and A23187 caused histamine release (median 26.7% range 6.2-62.8% and 32.1%, 7.7-56.8% respectively) which was significantly greater (P < 0.0001) than the spontaneous release (median 15.6%, range 4.1-33.4%), i.e. that in the absence of any stimulus. Substance P induced histamine release was via an energy dependent process and was blocked by preincubation with antimycin A. A significant correlation was observed between substance P induced release and spontaneous release but was not observed with A23187 induced release. Mast cell counts correlated significantly with substance P induced release but not with spontaneous or A23187 induced release. The substance P induced histamine secretion was elicited at similar concentrations to those used with rodent and human skin mast cells. Asthma is associated with increased numbers of mast cells which have both increased spontaneous and stimulated secretory responses. Thus, in vivo, the bronchoconstrictor action of substance P may in part result from activation of mast cells in the bronchial lumen.
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PMID:Substance P induces histamine release from human pulmonary mast cells. 753 43

We used genetically mast cell-deficient WBB6F1 W/Wv (W/Wv) mice and congenic WBB6F1 +/+ normal (+/+) mice to examine the role of mast cells in substance P-induced intestinal ion secretion. Isolated sheets prepared from segments of the midportion of the small intestine were studied in Ussing chambers. Substance P caused a dose-dependent increase in short-circuit current (Isc) that was approximately 50% less in intestine from W/Wv than from +/+ mice. Similar results were obtained for substance P-(4-11) (the COOH terminus) and substance P methyl ester [a selective neurokinin (NK)-1 agonist]. Histamine H1 or H2 antagonists reduced the Isc responses to substance P in intestine from +/+ mice but had no effect in intestine from W/Wv mice. In addition, reconstitution of intestinal mast cells in W/Wv mice by intravenous injection of +/+ bone marrow cells normalized the tissues' secretory responses to substance P or substance P methyl ester. However, in W/Wv and +/+ mice, the selective NK1 antagonist CP-96345 virtually abolished intestinal responses to substance P, and the responses were also markedly inhibited by neural blockade with tetrodotoxin. In contrast, in tetrodotoxin-pretreated intestine, histamine antagonism caused a further reduction in the responses to substance P only in +/+ mouse tissues. Taken together, our results suggest that the effects of substance P on intestinal Isc KN1 receptors but that the neuropeptide acts via effects on enteric nerves and mast cells. The data thus support the concept that mast cells and enteric nerves participate in the regulation of substance P-induced intestinal ion secretion.
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PMID:Substance P induces ion secretion in mouse small intestine through effects on enteric nerves and mast cells. 754 49

Histamine is known to cause edema and excitation of small-diameter primary afferent neurons. In the present study we wanted to investigate to which extent afferent neurons participate in histamine-induced edema and, subsequently, determine possible inhibitory effects of a tachykinin NK1 receptor and CGRP receptor antagonist on the histamine response. Intraplantar injection of histamine (0.5 mumol) into the rat hind paw caused a 34% increase of paw volume. In capsaicin-denervated rats, this effect of histamine was nearly abolished. The calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37), but not the tachykinin NK1 receptor antagonist SR140333, caused significant inhibition of the edema response. Further indication that CGRP can promote the histamine action was obtained in capsaicin-denervated rats, where co-injection of CGRP (0.3 pmol) increased the edema response to intraplantar histamine. In additional experiments, plasma protein extravasation in the paw skin was evaluated after close arterial infusion of histamine. Also in these experiments CGRP-(8-37), but not SR140333, significantly reduced the histamine effect. The observation that in the rat hind paw a CGRP receptor antagonist, but not a tachykinin NK1 receptor antagonist, attenuates histamine-induced vascular leakage raises the possibility that in some tissues CGRP receptor antagonists may be superior to tachykinin NK1 receptor antagonists in reducing histamine-induced neurogenic inflammatory responses.
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PMID:Histamine-induced edema in the rat paw--effect of capsaicin denervation and a CGRP receptor antagonist. 755 5

The present study was undertaken to investigate neural control of mouse small intestinal longitudinal muscle. Electrical field stimulation evoked acetylcholine- and neurokinin A-mediated contractile responses, whereas nitric oxide-mediated neurotransmission resulted in relaxation. The inflammatory mediators, histamine and leukotriene D4, contracted the longitudinal muscle preparation. Histamine-evoked contractions resulted from binding to histamine H1 receptors on non-neural cells of the small intestine. Leukotriene D4 played a role in neurokinin A-mediated excitation as the leukotriene D4 receptor antagonist, WY 48,252, reduced the response to nerve stimulation under noncholinergic conditions by almost 80%. In contrast, WY 48,252 had no effect on the response to exogenous neurokinin A, indicating that the response to this neurotransmitter is not mediated by leukotriene D4 release. Subthreshold concentrations of leukotriene D4 did not modify the response to neurokinin A, ruling out a synergistic relationship between these two agonists. Leukotriene D4 did not cause synaptic transmitter release through ganglionic stimulation, because its contractile effect was tetrodotoxin insensitive, and did not contribute to noncholinergic excitation through stimulation of neurokinin A release, as the neurokinin2 receptor antagonist, MEN 10,376, did not alter the response to leukotriene D4. Instead leukotriene D4 may modulate the release of neurokinin A from nerve endings during nerve stimulation.
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PMID:Neural control of mouse small intestinal longitudinal muscle: interactions with inflammatory mediators. 761 50

2H3 subline of rat basophilic leukemia (RBL-2H3) cells are mast cell analogs that lack responsiveness to nonimmunologic stimuli such as compound 48/80 and substance P. To determine if fibroblasts can influence this responsiveness, RBL-2H3 cells were cocultured with confluent monolayers of mouse 3T3 fibroblasts and assayed for secretagogue-induced histamine release. After 1 wk in coculture, RBL-2H3 cells began to respond to compound 48/80. Responsiveness reached a maximum at 2 wk in coculture and remained at this level for an additional 2 wk. Histamine release was specific, noncytotoxic, dose-dependent, and occurred even in the absence of extracellular Ca2+. No soluble factor from 3T3 cells was found that induced these alterations. Moreover, neither recombinant rat or mouse steel factor, at concentrations up to 250 ng/ml, was able to alter RBL-2H3 cell reactivity to compound 48/80. By 2 wk in coculture, RBL-2H3 cells also became responsive to substance P, although no changes in histamine content, Alcian blue+/safranin- staining or type of serine protease were detected. These results show that 3T3 fibroblasts cause an alteration in the functional repertoire of RBL-2H3 cells and that soluble steel factor cannot duplicate the effect.
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PMID:Mouse 3T3 fibroblasts induce rat basophilic leukemia (RBL-2H3) cells to acquire responsiveness to compound 48/80. 767 78

The frequent occurrence of acute death from pulmonary failure in experimental head injury studies on Sprague-Dawley rats prompted an investigation into the manner in which acute neurogenic pulmonary edema develops in these animals as a result of an applied fluid pressure pulse to the cerebral hemispheres. Studies were performed in adult animals using histamine H1 and H2 blocking agents, or in adult animals treated as neonates with capsaicin to destroy unmyelinated C-fibers. Recordings were made of either the pulmonary arterial or the right ventricular pressure, and the left atrial and femoral arterial pressures before, during, and after injury to provide a record of the hemodynamic response throughout the development of neurogenic pulmonary edema. Head injury triggered the almost immediate development of pressure transients with and without neurogenic pulmonary edema. All rats, regardless of treatment, reacted with nearly identical systemic arterial pressure responses; however, the pulmonary responses followed a time course that was independent of systemic arterial pressure changes. Acute neurogenic pulmonary edema was always associated with a substantial increase in pulmonary arterial and left atrial pressures; conversely, pressure increases of similar magnitude were not always associated with edema. Histamine H1 and H2 blockers significantly reduced the pulmonary pressure surges only in rats free of neurogenic pulmonary edema. All capsaicin-treated rats showed suppressed pulmonary pressure responses, normal lung water content, elevated lung surface tension, and significantly reduced levels of immunoreactive substance P in the spinal cord and vagus nerve. While the pressures cannot clarify how edema influences the observed hemodynamics, they do not support the view that edema is the direct consequence of pulmonary hypertension. It is proposed that neurogenic pulmonary edema is a functional disturbance provoked by adverse stimuli from outside the lungs and that in the rat the primary afferent fiber is essential to the production of this entity.
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PMID:Effect of neonatal capsaicin treatment on neurogenic pulmonary edema from fluid-percussion brain injury in the adult rat. 768 Jul 9

To determine how the microenvironment in which mast cells are located may influence their function, we explored the effects of fibronectin and fibroblasts on histamine secretion in vitro from a mast cell model, the rat basophilic leukemia (RBL-2H3) cell line. RBL-2H3 cells bound specifically to fibronectin-coated surfaces. Binding was maximal by 1 hour, was not detectable at 0 degrees C or in the absence of Ca++, and was inhibited by preincubating the cells with a synthetic peptide containing the RGD sequence. Adherence to fibronectin stimulated RBL-2H3 cell spreading with a concomitant reorganization of the cytoskeleton and a repositioning of the cytoplasmic granules to the cell periphery. Although adherence to fibronectin did not by itself induce histamine release, when stimulated by either immunologic or non-immunologic means, fibronectin-adherent cells released dramatically more histamine than cells plated in wells coated with BSA only. Thus, RBL-2H3 cells bind specifically to fibronectin, and in so doing are stimulated to undergo changes in morphology and enhanced responsiveness to secretory stimuli. RBL-2H3 cells grown in coculture with 3T3 fibroblasts, but not RBL-2H3 cells grown alone, became responsive to the polymeric synthetic secretagogue Compound 48/80 and the neuropeptide Substance P. Maximum sensitivity to Compound 48/80 was attained by the second week in coculture. Histamine release was dose-dependent, noncytotoxic and occurred even in the absence of extracellular Ca++. Contact between the 2 cell types appeared to be a critical factor. RBL-2H3 cells, separated from 3T3 cells by a 0.45 micron filter, failed to secrete histamine in response to Compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mast cells and their microenvironment: the influence of fibronectin and fibroblasts on the functional repertoire of rat basophilic leukemia cells. 768 21

To investigate the mechanism and neural control of the nasal secretion, we observed the isolated rat nasal mucosa by video-enhanced differential interference contrast microscopy. This technique allowed us to visualize abrupt changes of the individual granules leading to degranulation in the acinar cells and in epithelial goblet cells during secretory stimulation. This image provided evidence that exocytosis is the major mode for regulated secretion in the nasal acinar cells and goblet cells. Acetylcholine (ACh, 0.1-100 microM), substance P (SP, 0.1-10 microM), and vasoactive intestinal peptide (VIP, 0.1-1 microM) induced exocytotic responses and shrinkage of the acinus in a concentration-dependent manner. The effects of ACh (10 microM) on the acinus were clearly inhibited by atropine (5 microM), but the effects of SP (1 microM) and VIP (1 microM) were not. The acinar shrinkage always started before exocytosis, suggesting that the fluid secretion precedes the mucus release. In goblet cells, SP (1 microM) and ACh (10 microM) increased the frequency of exocytotic responses significantly, suggesting that these substances truly play the role of a neurotransmitter for nasal secretion. Histamine (HIST) induced no visible response. The effect of HIST on secretory cells may be neuronally mediated in vivo.
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PMID:Neurotransmitter-induced exocytosis in goblet and acinar cells of rat nasal mucosa studied by video microscopy. 769 Jan 90

Applications of histamine to neurons in slices of trigeminal root ganglia (guinea-pig) produced slow changes in the steady-state membrane potentials and input resistances. Several types of response to histamine could be distinguished: (i) depolarizations accompanied by an increase, a decrease or no change in input resistance; (ii) small hyperpolarizations associated with a decreased or unchanged input resistance; and (iii) combined hyper- and depolarizations. The amplitudes of all response types waned during prolonged applications of histamine. The depolarizing responses to histamine appeared to depend on the presence of outward rectification in the region of the initial resting potential; neurons which possessed linear current-voltage relationships near the initial resting potential were depolarized by > 10 mV, whereas neurons with outward rectification near rest showed smaller depolarizing responses. Histamine also reduced the magnitude of the long-duration spike afterhyperpolarizations which had been attributed in the ganglionic neuron to a Ca(2+)-activated K+ conductance mechanism. Application of substance P, another possible neuromodulator in the trigeminal system, had depolarizing, desensitizing actions similar to those of histamine. Substance P and histamine did not cross-desensitize during prolonged applications. Histamine-induced depolarizations were unchanged under zero Mg2+ extracellular conditions, in contrast to a dependency of the substance P-induced effects on external Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Histamine actions and comparison with substance P effects in trigeminal neurons. 769 Sep 11


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