Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P is an undecapeptide found in multiple sites throughout the central and peripheral nervous systems including small unmyelinated (type C) cutaneous nerve fibers. Previous studies demonstrated that antidromic stimulation results in substance P (SP) release from nerve endings, SP stimulates histamine release (HR) from rat mast cells in vitro, and intradermal SP in humans produces wheals identical to those induced by histamine. These studies suggest a possible role for SP as a link between neurologic events and cutaneous mast cell-mediated reactions. We therefore investigated SP-induced HR in an in vitro preparation of human skin mast cells. Human foreskin sections were incubated with varying concentrations of SP. Histamine was assayed using automated fluorimetry and release was calculated as a percentage of total tissue histamine. Substance P caused dose-dependent HR over a range from 10(-5) M (1.3%) to 5 X 10(-4) M (25.1%). Histamine release was optimal at 3 mM calcium and was blocked by pretreatment with calcium chelation. Naloxone failed to block HR. These studies suggest that HR from skin mast cells by SP may play a role in neural modulation of poorly understood inflammatory skin conditions.
 ...
PMID:Substance P-induced histamine release in human cutaneous mast cells. 243 55

Substance P is a representative of a group of amphiphilic neuropeptides which act as mast cell secretagogues. Our experiments with some new substance P derivatives suggest that these effects are dependent on two structural elements: (i) a hydrophobic chain which is not essentially a peptide, and (ii) a hydrophilic part with two positively charged amino acids. The mast cell triggering effect is unlikely to be mediated by a selective substance P receptor, but has strong similarities to the mode of action of polycations.
 ...
PMID:Mast cell activation--a receptor-independent mode of substance P action? 244 34

The flare response in skin largely depends on an intact primary sensory fiber, the C-fiber. We measured the flare response to the intradermal injection of substance P, histamine, and capsaicin in control subjects and in diabetic patients with and without clinically obvious polyneuropathy. The neuropathic diabetic patients had a reduced flare response to substance P, histamine, and capsaicin, compared with control and nonneuropathic diabetic subjects. The smaller flare response in the neuropathic diabetics after capsaicin administration suggested a dysfunction of the peripheral component of the C-fiber. Alternatively, dysfunction of the mast cell or vascular reactivity may contribute to the diminished flare. Because C-fibers participate in nociception in addition to the flare response, the findings of this study, by a method that permits a quantifiable measurement of the function of peripheral sensory neurons in diabetic subjects, has potential usefulness in evaluating sensory neuropathy in diabetic patients.
 ...
PMID:Diminished flare response in neuropathic diabetic patients. Comparison of effects of substance P, histamine, and capsaicin. 244 7

Our studies have clearly shown that neuropeptides have a profound effect on immunoglobulin synthesis both in vivo and in vitro. The effects varied according to the neuropeptide added or the tissue from which the lymphocytes were obtained. Substance P caused the most pronounced enhancement of both functions, especially in Peyer's patch cells, where it selectively increased IgA synthesis. Somatostatin was inhibitory, and the effect of vasoactive intestinal peptide varied according to the source of the cells. We have previously shown that neuropeptides also cause mast cell secretion and that only substance P was effective in this regard on intestinal mucosal mast cells. Therefore, we looked for microanatomic relationships between peptidergic nerves and immune effector cells. Mast cells appear to have structural associations with neuropeptides-containing nerves in the intestine. Nerve growth factor, known to promote the growth of sensory afferent and sympathetic nerves, has significant direct effects on mast cells. In vitro, this substance caused enhanced antigen mediated histamine release and, in vivo, extensive mast cell hyperplasia. Also, in humans, we were able to produce increased numbers of mast cell/basophil colonies from peripheral blood in the presence of nerve growth factor.
 ...
PMID:Neuropeptides and immunity. 244 42

The peptides substance P (SP) and vasoactive intestinal peptide (VIP) released from peptidergic neurons have potent effects on gland secretion and on smooth muscle tone. Because mast cells release proteases during degranulation, and are located in many of the same tissue microenvironments into which SP and VIP are released, we wished to examine whether mast cell proteases, by cleaving and thus inactivating these peptides, could modulate their effects. We used active site-titrated preparations of the two major neutral proteases of mast cell granules, tryptase and chymase, to determine the sites and rates of cleavage of SP and VIP. The proteases were purified from dog mastocytomas. Tryptase cleaved VIP rapidly at two sites with a kcat/Km of 2.2 X 10(5) sec-1 M-1, but had no effect on SP. Chymase cleaved both SP and VIP at primarily a single site with kcat/Km of 3.9 X 10(4) and 5.4 X 10(4) sec-1 M-1, respectively. Thus, these data show that mast cell proteases degrade SP and VIP. The differences in peptidase activity between tryptase and chymase suggest that the consequences of protease release could vary according to mast cell protease phenotype and location in various tissues and species. Tryptase, by cleaving the bronchodilator VIP but not the bronchoconstrictor SP, might promote bronchial hyper-responsiveness in asthma by decreasing the nonadrenergic neural inhibitory influence mediated by VIP. In skin and other tissues, chymase might interrupt axon reflex-mediated neurogenic inflammation by cleaving SP.
 ...
PMID:Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. 244 73

We have compared the ability of anti-IgE, calcium ionophore A23187, substance P, compound 48/80, poly-L-lysine, and morphine to release histamine from mast cells of human skin, lung, adenoids, tonsils, and colon. Use of a single collagenase/hyaluronidase dispersion technique for all tissues has allowed comparisons of reactivity to be made that are free from methodological variations. Mast cells from all tissues examined secreted histamine in response to anti-IgE and calcium ionophore A23187. However, only skin mast cells were responsive to substance P, compound 48/80, poly-L-lysine, and morphine. Activation of human skin mast cells by these nonimmunologic stimuli clearly distinguishes them from the mast cells of human lung, adenoids, tonsils, and colon and is indicative of functional heterogeneity within the human mast cells population. We propose that the presence of functional receptor sites for neuropeptides and basic compounds on skin mast cells that are not present in mast cell populations from mucosal or lymphoid sources reflects a specialized role for these cells in vascular homeostasis.
 ...
PMID:Human mast cell heterogeneity: histamine release from mast cells dispersed from skin, lung, adenoids, tonsils, and colon in response to IgE-dependent and nonimmunologic stimuli. 245 Jan 14

Biomicroscopic experiments have shown that the N-terminal fragment of substance P (SP1-4), when applied to the rat mesentery, has a considerably lower injuring effect than substance P (SP1-11) itself. SP1-4 activity, as compared to SP1-11 activity regarded as 1, was 0.007 in case of microcirculatory disturbances and venular permeability increase and 0.0007 in case of mast cell degranulation increase. The data obtained suggest that the slightest damaging effect of SP1-4 on microcirculation is combined with anti-stress activity.
 ...
PMID:[Effect of the N-terminal fragment of substance P on the microcirculatory system]. 245 44

The 37-amino-acid calcitonin gene-related peptide (CGRP) occurs as a result of alternative processing of mRNA from the calcitonin gene. The potency of CGRP as a vasodilator and the occurrence of the peptide in nerves associated with blood vessels suggest an important role for CGRP in the regulation of blood flow. The finding that CGRP induces protracted vasodilatation when administered extra-vascularly, to mimic release from nerves, has led us to investigate how the vasodilator activity of CGRP is controlled in vivo. CGRP is often co-localized with substance P in C-fibre nerves. Here, we demonstrate that injection of CGRP with substance P into human skin converts the long-lasting vasodilatation induced by CGRP into a transient response. Experiments in animals reveal that the phenomenon is dependent on the action of proteases from mast cells stimulated by substance P. The results reveal a new regulatory interaction between two neuropeptides and provide evidence for an in vivo role for mast cell proteases.
 ...
PMID:Substance P regulates the vasodilator activity of calcitonin gene-related peptide. 245 10

The interaction of substance P (SP) with specific receptors in intact lung tissue was autoradiographically visualized, using slide-mounted tissue sections of rat lung tissue. SP receptors are highly concentrated in the central airways and are not detectable in peripheral bronchi, vessels, and alveoli. Within central airways, receptor distribution is most concentrated in the epithelium and small vessels in the lamina propria. Smooth muscle in airway or blood vessel walls expressed no detectable SP receptors. Immunohistochemical staining for SP revealed SP-containing nerves in the same areas where the receptors are localized. Displacement curves of SP bound to rat lung indicated that the C-terminal fragment was much more effective than the N-terminal fragment at competing for SP binding. Injection of 0.3 to 30 nmol/kg SP dramatically increased vascular permeability in the trachea and to a lesser extent in the hilus. Peripheral lung failed to respond to SP with increased vascular permeability unless toxic concentrations of SP were employed. SP increased the transudation of protein into the trachea within 5 min of injection, and the extravasated protein persisted through at least 2 h. Both SP and SP(3-11) were capable of stimulating increased vascular permeability, but SP(1-4) was inactive. SP caused mast cell degranulation as reflected in increased plasma histamine levels after SP or SP(3-11) injection, but SP(1-4) had no effect. In order to determine if histamine release caused by SP contributed to the vascular permeability response, the effects of H1 and H2 antihistamine treatment were studied.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Substance P: the relationship between receptor distribution in rat lung and the capacity of substance P to stimulate vascular permeability. 246 77

A hypothesis is presented that mast cells in and below the epithelium of the respiratory tract show functional association with nerves to form a homeostatic regulatory unit. During inflammation, mast cells may arise in situ as well as by infiltration because epithelium contains both mast cell precursors and produces factors that support their growth in vitro. Structural studies show that mast cells associate with nerves in the lung. Using a tissue culture model, we showed that sympathetic nerves formed lasting contacts with rat basophilic leukemia (RBL) cells. Electrophysiologic studies showed that nerve contact increases RBL membrane conductance, which can be mimicked by exogenous substance P (SP). Experiments with sensitized rat tracheal mucosa in Ussing chambers showed functional evidence of interaction of mast cells with SP-containing nerves: changes in short circuit current caused by antigen were blocked by the mast cell stabilizer doxantrazole and reduced by 50% by neonatal pretreatment with capsaicin. Experiments in vivo showed that lung clearance of the aerosol probe 99mTc-DTPA was increased by antigen challenge in sensitized rats. This was blocked by neonatal capsaicin treatment, again implicating SP-containing nerves. Therefore, we conclude that the functional association of mast cells with nerves is an important mechanism in regulating the local epithelial environment.
 ...
PMID:Inflammatory cells and the epithelium. Mast cell/nerve interactions in the lung in vitro and in vivo. 246 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>