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)

Previously we established that in vitro NO2 exposure induced inhibition of histamine release from rat peritoneal mast cells (PMC) stimulated with secretagogues such as compound 48/80 or substance P. To further explore the effects of NO2 exposure on mast cells, we investigated whether the addition of an antioxidant agent, 2-mercaptoethanol (2-ME), can prevent NO2-induced inhibition of mediator release from PMC. Histamine release from 5 ppm NO2-exposed PMC stimulated with 10 and 20 microM substance P was significantly inhibited compared with that from the controls. beta-Hexosaminidase release from 5 ppm NO2-exposed PMC stimulated with 20 microM substance P was also significantly inhibited. However, the inhibition of both histamine and beta-hexosaminidase release from exposed PMC was diminished by the addition of 5 mM 2-ME during NO2 exposure. Although IgE-mediated histamine release from NO2 exposed PMC was markedly inhibited, the addition of 5 mM 2-ME during NO2 exposure induced no inhibition of histamine release. These results suggest a possible relationship between NO2-induced inhibition of mast cell mediator release and production of free radicals by the action of NO2.
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PMID:An antioxidant agent prevents NO2-induced inhibition of mast cell mediator release: evidence that the mechanism involves free radicals. 170 82

Primary cultures of rat trigeminal ganglion cells were exposed to histamine, and the intracellular free-calcium concentrations, [Ca2+]i, were measured by the calcium-sensitive dye fura-2. Histamine (10(-6)-10(-2) M) increased the [Ca2+]i of the neurons. Pretreatment of the cells with histamine H1-receptor blocker pyrilamine (10(-4) M), or chelation of extracellular calcium, abolished the response; however, the response was not altered by pretreatment with H2-blocker cimetidine (10(-2) M). Thus, the increase in [Ca2+]i was due to the influx of extracellular calcium mediated by H1-receptor. Immunocytochemical analysis showed that these cultured cells that respond to histamine were identically calcitonin gene-related peptide (CGRP)- or substance P (SP)-like immunoreactive. The findings suggested that histamine released from mast cells directly affected CGRP- and SP-containing sensory neurons via H1-receptor, which convey nociceptive information.
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PMID:Histamine acts directly on calcitonin gene-related peptide- and substance P-containing trigeminal ganglion neurons as assessed by calcium influx and immunocytochemistry. 170 3

Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer.
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PMID:Skin test reactivity in patients suffering from lung and breast cancer. 171 Jun 31

1. Endothelium-dependency of vasodilator responses was compared in helical strips of monkey cerebral and superficial temporal arteries contracted with prostaglandin F2 alpha. Acetylcholine produced an endothelium-dependent relaxation in the temporal arteries, but did not consistently alter the tone of cerebral arteries. 2. Adenosine 5'-triphosphate (ATP) produced a transient contraction followed by a relaxation in the temporal and cerebral arteries; removal of the endothelium partially attenuated the relaxation of the cerebral arteries and markedly suppressed the relaxation in the temporal arteries. The dependency of adenosine 5'-diphosphate (ADP)-induced relaxations on the endothelium was also greater in temporal arteries than in cerebral arteries. 3. Histamine-induced relaxations in the temporal arteries were independent of the endothelium and were reversed to contractions by cimetidine. Cerebral arterial relaxations induced by histamine were partly dependent on the endothelium. Relaxations caused by substance P were reversed to contractions by removal of the endothelium in the temporal arteries, whereas the peptide did not consistently alter the tone of cerebral arteries. 4. The Ca2+ ionophore, A23187, relaxed the temporal and cerebral arteries to a similar extent; removal of the endothelium abolished these relaxations. Glyceryl trinitrate elicited similar relaxation of cerebral and temporal arteries, and these were independent of the endothelium. 5. These findings clearly indicate heterogeneity in the endothelium-dependency of several vasodilator responses in monkey intra- and extracranial arteries, although the ability of these arteries to respond to A23187 and glyceryl trinitrate does not appear to differ. The heterogeneous responses observed so far could therefore be due to different distributions of receptors or to variation in receptor-effector coupling in endothelial cells.
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PMID:Comparison of endothelium-dependent responses of monkey cerebral and temporal arteries. 171 6

The action of histamine on human dermal microvascular endothelial cells and modulation of its effects by the cytokine interleukin-1 and the vasoactive neuropeptide substance P have been investigated. Histamine (10(-6)-10(-3) M) induces release of prostaglandin E2 in a concentration- and time-dependent manner. Prostaglandin E2 release is facilitated principally by histamine H1 receptors as the H1 receptor antagonist pyrilamine attenuates prostaglandin E2 release whereas the H2 receptor antagonist cimetidine only slightly reduces release. In contrast to other cells, the histamine/receptor interaction is not associated with increased intracellular accumulation of the cyclic nucleotides, cyclic AMP, or cyclic GMP. Interleukin-1 induces a concentration-dependent release of prostaglandin E2 following 24 h incubation. However, substance P does not increase release of prostaglandin E2 above baseline. In cells incubated with 1 U/ml human recombinant interleukin 1 alpha for 24 h prior to stimulation with histamine (10(-5)-10(-3) M) for 30 min, there is a significant potentiation of histamine-induced release of prostaglandin E2 (p less than 0.05). Using a solubilized cell sonicate prepared from human dermal microvascular endothelial cells incubated with 1 U/ml human recombinant interleukin 1 alpha for 24 h, conversion of exogenous arachidonic acid into prostaglandin E2 increased by 60.19 +/- 18.28%. Cycloheximide partially reduces the increased conversion but completely blocks interleukin-1-induced release of prostaglandin E2 from intact cells. Substance P does not potentiate histamine-induced release of prostaglandin E2 or increase arachidonic acid conversion. These results demonstrate that human dermal microvascular endothelial cells are responsive to histamine and that interleukin-1, but not substance P, can potentiate histamine-induced release of prostaglandin E2. Interleukin-1 appears to act, at least in part, by regulating the availability of free arachidonic acid. Interactions between histamine and interleukin-1 may be important in the modulation of inflammatory reactions in skin.
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PMID:Responses of human dermal microvascular endothelial cells to histamine and their modulation by interleukin 1 and substance P. 171 8

Mast cells of the human skin not only release mediators following immunological activation, but may also be stimulated to release histamine by the neuropeptides substance P, vasoactive intestinal polypeptide and somatostatin or by other basic secretagogues such as morphine, poly-L-lysine and compound 48/80. Release of histamine under these conditions is rapid and accompanied by minimal generation of the eicosanoids, prostaglandin (PG)D2 and leukotriene (LT)C4. Transient elevations of intracellular calcium are associated with mediator secretion induced by both stimuli, that induced by anti-IgE being derived from extracellular sources through channels in the plasma membrane while that stimulated by neuropeptides is mobilized intracellularly. Similarly, elevations of intracellular cyclic adenosine monophosphate (AMP) induced by anti-IgE occur only in the presence of extracellular calcium whereas with substance P elevations are apparent even in the absence of extracellular calcium. With the latter stimulus, histamine release is complete before the peak cyclic AMP is achieved. Histamine release stimulated by both secretagogues is unaffected by sodium cromoglycate or nedocromil sodium but is reduced by both salbutamol and isobutylmethylxanthine. Despite these biochemical and temporal differences, degranulation induced by both secretagogues proceeds by compound exocytosis which is indistinguishable under the electron microscope.
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PMID:Mediator secretion from human skin mast cells provoked by immunological and non-immunological stimulation. 172 14

Human blood polymorphonuclear neutrophils (PMN) are thought to be involved in the pathogenesis of asthma through their recruitment into the bronchoalveolar lumen and the lung by local release of chemotactic factors. Therefore chemotactic activities of several mediators (PAF, histamine and three neuropeptides substance P, VIP and a somatostatin analog) were compared on blood PMN from both healthy subjects (HS) and asthmatic patients (AP). The maximal response to PAF was significantly different (P less than 0.05) with cells from both groups. Moreover activity for the HS peaked at 10(-6) M, whereas the AP showed peak chemotactic activity at 10(-8) M. Histamine had no chemoattractant effect on PMN. Substance P did not induce PMN locomotion, whereas VIP induced a chemotactic response in a dose-dependent manner, particularly with cells from HS as compared to those from AP. BIM 23014 (a somatostatin analog) exhibited chemotactic activity which was also more pronounced with PMN from HS as compared to those from AP. Our findings showed that blood PMN could be involved in asthma through their heightened locomotor reactions to mediators which are known to be released locally by activated cells in bronchoalveolar lumen.
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PMID:Neutrophil chemotactic activity of PAF, histamine and neuromediators in bronchial asthma. 172 27

Effects of spantide ([D-Arg1,D-Trp7,9,Leu11]substance P) on coronary resistance vessels were studied in isolated guinea pig hearts perfused at constant rate with isotonic buffer containing 20 or 40 mM KCl. Spantide (1 microM) caused a 20-fold rightward shift of the substance P (SP) dose-response curve for vasodilation with no change in maximum (KB = 5.3 x 10(-8) M). Bolus injections of 0.25 to 250 pmol spantide had no effect, but higher doses caused a brief vasodilation followed by a larger, more prolonged vasoconstriction. Histamine produced similar changes in perfusion pressure. Antihistamines (H1 and H2) reduced or blocked responses to spantide and histamine. These findings indicate spantide is a competitive antagonist to SP in guinea pig coronary resistance vessels. In addition, high doses of spantide can cause prominent vascular effects which are mediated by histamine.
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PMID:Effects of spantide on guinea pig coronary resistance vessels. 172

A physiological role of substance P (SP) in inflammatory reaction was examined in the rat incisor pulp and inferior lip. SP content in pulps and lips significantly increased after antidromic stimulation of the inferior alveolar nerve. Following the same stimulation, vascular permeability also increased significantly in pulps and lips, and this permeability response was significantly inhibited by an SP-antagonist. Morphine reduced the permeability response to antidromic stimulation in pulps but had no effect in lips. N-methyl levallorphan (a peripherally selective narcotic antagonist) prevented the morphine-induced reduction, and was more potent than naloxone. Morphine caused a marked increase of SP content in pulps following antidromic stimulation of the inferior alveolar nerve but failed in lips. These suggest a possibility that a peripheral SP release-suppressive mechanism by opiates may exist in pulps but not in lips. The permeability response to antidromic stimulation was also reduced by aspirin and a bradykinin antagonist in both of the tissues, indicating that prostaglandin and bradykinin may be related to this response. Since mepyramine and methysergide inhibited the permeability response in lips but were inactive in pulps, there is a difference in participation of histamine and serotonin between the two tissues. SP injection into the dental pulp and lip induced dye leakage. This response was inhibited by compound 48/80 pretreatment in lips whereas it was resistant in pulps. Histamine content in lips decreased significantly after antidromic stimulation and compound 48/80 pretreatment, but it was not changed in pulps. The present results suggest that in lips after being released from the peripheral sensory nerve endings SP may act on vascular system through histamine release from mast cells, while in pulps SP may directly cause vascular response because mast cells may be few or not exist.
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PMID:[Role of substance P on neurogenic inflammation in the rat dental pulp and inferior lip]. 172 14

Histamine is thought to be a neuroactive substance in the brain and have various physiological functions such as biological rhythms and autonomic regulation. It can be speculated, therefore, that synaptic inputs to histaminergic neurons may exert powerful influences upon those histaminergic functions. Synaptic connections between histaminergic neurons and substance P (SP) or neuropeptide Y (NPY) afferents in the caudal magnocellular nucleus (CM) of the hypothalamus were examined using an immunoelectron microscopic mirror method. SP-immunoreactive (SR-IR) and NPY-immunoreactive (NPY-IR) terminals made synaptic contacts with histidine decarboxylase immunoreactive (HDC-IR) neurons. Furthermore, the relationship between HDC-IR neurons and glycine receptor-immunoreactive (Gly-R-IR) profiles was examined in the CM by the same method as described above. A low to moderate density of dot-like Gly-R-IR profiles was seen at the light microscopic level. At the electron microscopic level, HDC-IR neurons were identified to have Gly-R immunoreactivity at postsynaptic sites on their somata. Our findings suggest that SP, NPY and possible glycinergic afferents exert monosynaptic influences on the central histaminergic neuronal system.
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PMID:Synaptic inputs to histaminergic neurons in the rat posterior hypothalamus. 179 64


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