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)

In this review, only a few questions concerning the mechanism(s) of action of sodium cromoglycate in asthma have been considered. The large number of cells and mediator pathways where sodium cromoglycate may have pharmacological effects are depicted. In addition to its mast cell effect, sodium cromoglycate is also inhibitory to macrophages, eosinophils, monocytes and platelets, which are all important components in the inflammatory response of asthma. From studies with bradykinin and sulphur dioxide it is also known that the drug can block afferent discharges along non-myelinated nerves. Although the ability of sodium cromoglycate to block late phase responses and acquired hyper-reactivity is not questioned, to what extent its therapeutic efficacy can be accounted for by actions on these leukocytes and reflex pathways is not known. When administered to patients with asthma, sodium cromoglycate results in symptomatic improvement, but there is still much to be learned about its mode of action.
 ...
PMID:Reflections on the mechanism(s) of action of sodium cromoglycate (Intal) and the role of mast cells in asthma. 251 46

Adenosine, which may be formed by all cells during relative energy or oxygen deficit, may act as an autocoid by modifying the function of other cells in the local environment. In asthmatic, but not normal, subjects, inhalation of adenosine causes a marked bronchoconstriction which may be reduced by the purinoceptor antagonist theophylline, sodium cromoglycate, nedocromil sodium, histamine, H1-antagonists and cyclo-oxygenase inhibitors. Repeated exposure to adenosine induces a state of tachyphylaxis and cross-tachyphylaxis with exercise-induced bronchoconstriction but not with that provoked by allergen. Although the mechanisms by which adenosine induces changes in airways function are not clear, it is suggested that it has an indirect effect, possibly by up-regulating bronchoconstrictor factors already present in asthma such as mast cell mediator release or neuronal reflexes.
 ...
PMID:Adenosine as a pro-inflammatory mediator in asthma. 252 Apr 85

To investigate the mechanism of bronchial spasm induced by inhalation of ultrasonically nebulised distilled water (UNDW) ultrasonically nebulised solutions including hypoosmolar (distilled water, 0.3% NaCL) isoosmolar (0.9% NaCL) and hyperosmolar solutions (2.7% NaCL, 3.6% NaCL, 4.6% KCL 22.2% dextrose) were used for challenge test in 12 asthmatic patients and 10 healthy subjects as controls. The dose of solution required to induce a 20% reduction in FEV 1 (FD 20-FEV 1) was recorded. In another 10 asthmatic patients, a challenge with UNDW was conducted after pretreatment with sodium cromoglycate (SC), Ipratropine Bromide (IB) to investigate the protective effect of the two medicines. The results showed that distilled water and three hyperosmolar solutions which were of the same osmotic pressure (3.6% NaCL, 4.6% KCL and 22.2% dextrose) were most potent in inducing bronchoconstriction, and no significant difference in PD 20-FEV 1 was found among them 0.3% and 2.7% NaCL were next and 0.9% NaCL was the least potent. Normal subjects showed no response to the solutions. The SC gave significant protection to nine of the ten patients, and IB gave it to five of the ten. Our results indicate that a change in the osmolarity of the fluid lining the respiratory tract may be an important determinant of the airway response; sodium cromoglycate which inhibits the mediator release of mast cell can reduce the airway response to UNDW.
 ...
PMID:[Effects of nebulized distilled water on tracheal reaction in asthmatic patients]. 253 83

We have developed a model of asthma in conscious guinea-pigs in which inhalation challenge with specific allergen induces both early and late phase reductions in specific airways conductance. Analysis of cells removed from the airways by bronchoalveolar lavage showed the presence of a neutrophilia, which reached a maximum at 17 hours, and an eosinophilia which developed more slowly, still increasing at 72 hours. Nedocromil sodium inhaled before challenge inhibited both the early and late phase responses. In contrast, the beta-adrenoceptor stimulant, salbutamol, inhibited only the early phase. When inhaled 6 hours after challenge, i.e. between the early and late phase responses, the late phase bronchoconstriction was prevented by nedocromil sodium but only partially by salbutamol. Evidence that the neutrophilia was not functionally associated with the late response was gained from the observations that it was inhibited by both nedocromil sodium and salbutamol, whereas only nedocromil sodium blocked the late phase airways response. When administered 6 hours after challenge, nedocromil sodium reduced eosinophil accumulation at 72 hours in parallel with inhibiting a secondary late response at this time. These results demonstrate that nedocromil sodium is able to prevent both early and late phase reductions in airways function in an animal model of allergic asthma. Whereas inhibition of the early response may reflect an effect on mast cell mediator release, the effects of nedocromil sodium on the late response and on eosinophil accumulation are strongly suggestive of an anti-inflammatory effect within the lung.
 ...
PMID:Effect of nedocromil sodium on early and late phase responses to allergen challenge in the guinea-pig. 254 59

The antiasthmatic agent, sodium cromoglycate, owes its discovery to a series of antigen challenge tests carried out during the 1960s by an asthmatic, Roger Altounyan, on himself. Until recently, research efforts to identify new antiasthma drugs have relied heavily on screening methods which involved passively-sensitised mast cells. In theory these tests, such as rat passive cutaneous anaphylaxis, appeared relevant and showed sodium cromoglycate to have a stabilising effect on the mast cell membrane. In practice no new drugs were discovered, since this type of activity in animal models was not predictive of antiasthmatic potential. A more relevant research programme has subsequently evolved, which attempts to approach more closely the conditions prevailing in the asthmatic lung. The use of a model of immune lung inflammation in macaque monkeys in conjunction with a model of bronchial hyper-reactivity in the dog has been successful in producing the new compound, nedocromil sodium, which is proving to be an effective addition to the drugs available for the treatment of inflammatory diseases of the airways.
 ...
PMID:Development of preclinical models for testing antiasthma drugs. 254 61

The demonstration of a specific receptor for IgE on non-mast cell or basophil leucocytes, such as mononuclear phagocytes, eosinophils and platelets, suggests that these cells may participate directly in immunological disorders of allergy. In this study, inhibition by nedocromil sodium of IgE-dependent activation of human alveolar macrophages, blood monocytes and platelets was investigated. Nedocromil sodium produced an inhibition of IgE-mediated generation of cytotoxic molecules from monocytes and platelets together with a concomitant inhibition of their oxidative metabolism, measured by chemiluminescence. In addition, nedocromil sodium reduced the ability of alveolar macrophages to synthesise and release mediators, estimated by beta-glucuronidase activity. Furthermore, nedocromil sodium inhibited the abnormal response to aspirin of platelets from aspirin-sensitive asthmatics at therapeutic concentrations. These studies confirm that nedocromil sodium acts on a cell compartment other than the classical mast cell population in IgE-dependent allergy and asthma.
 ...
PMID:Nedocromil sodium inhibition of IgE-mediated activation of human mononuclear phagocytes and platelets from asthmatics. 254 66

We have measured the steady-state tryptophan fluorescence spectrum of cytochrome oxidase in its oxidized and fully reduced states. Reduction of the oxidized enzyme by sodium dithionite causes an apparent shift in the fluorescence emission maximum from 328 nm, in the oxidized enzyme, to 348 nm, in the reduced enzyme. This spectroscopic change has been observed previously and assigned to a redox-linked, conformational change in cytochrome oxidase [Copeland, R. A., Smith, P. A., & Chan, S. I. (1987) Biochemistry 26, 7311-7316]. When dithionite-reduced enzyme sits in an open cuvette, the enzyme returns to the oxidized state, and the fluorescence maximum shifts back to 328 nm. However, the time course of the fluorescence change does not follow the redox state of the enzyme, monitored spectrophotometrically at 445,605, and 820 nm, but follows the disappearance of dithionite, which absorbs at 315 nm. Moreover, when the fluorescence emission spectrum of the dithionite-reduced enzyme is corrected for the absorbance due to dithionite, the fluorescence maximum is found 2 nm blue shifted, relative to that of the oxidized enzyme, at 326 nm. This dithionite-induced, red-shifted steady-state tryptophan fluorescence is also seen with the non-heme-containing enzyme carboxypeptidase A. The tryptophan emission spectrum of untreated carboxypeptidase A is at 332 nm, whereas in the presence of dithionite the emission spectrum of carboxypeptidase A is at 350 nm. When corrected for the absorbance of dithionite, the tryptophan emission maximum is at 332 nm. We have also used the photoreductant 3,10-dimethyl-5-deazaisoalloxazine (deazaflavin) to reduce cytochrome oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Characterization of reductant-induced, tryptophan fluorescence changes in cytochrome oxidase. 255 93

Treatment of "difficult" asthma requires good doctor-patient communication, patient education, and attention to precipitating factors as well as an aggressive drug regimen. Specific medications include inhaled sympathomimetic and anti-cholinergic bronchodilators, inhaled, oral and/or intravenous corticosteroids and, in certain circumstances, mast cell stabilizing drugs such as cromolyn sodium. The use of systemic theophyllines is currently undergoing critical reevaluation. There have been a number of recent developments in the search for steroid-sparing agents and drugs that inhibit inflammatory mediators felt to be important in the pathophysiology of asthma. Most of these drugs are still undergoing evaluation in multicentre clinical trials. The newer antiinflammatory agents, methotrexate and gold, should probably not be used on a routine basis except as part of randomized, ethically approved clinical trials.
 ...
PMID:Treatment of the recalcitrant asthmatic. 257 88

The clinical manifestations of allergic rhinitis are the result of an immune-mediated process after exposure of a sensitized individual to airborne allergens. The primary symptomatology includes nasal congestion, rhinorrhea, nasal and conjunctival pruritus, and sneezing. Principles of management include allergen avoidance, palliative therapy, immunotherapy, and pharmacotherapy. Oral decongestants stimulate alpha-adrenergic receptors in the nasal cavity, resulting in vasoconstriction and decreased edema. Oral antihistamines block histamine1 (H1) receptors, and may relieve rhinorrhea, sneezing, and nasal and conjunctival pruritus. Topical decongestants have a local effect on adrenergic receptors in the nasal mucosa, resulting in rapid, marked vasoconstriction. Intranasal corticosteroids inhibit mediator release from mast cells and basophils, and reduce edema of the nasal mucosa. Dexamethasone sodium phosphate, beclomethasone dipropionate, and flunisolide are currently available for intranasal administration. Cromolyn sodium inhibits allergen-induced degranulation and mediator release from sensitized cells, and is useful primarily as a prophylactic agent. Several agents, including the corticosteroids budesonide and flucortin butylester, the mast cell-stabilizing agent nedocromil sodium, the anticholinergic agent ipratropium bromide, and the H1 receptor antagonist levocabastine are being investigated for intranasal use in the management of allergic rhinitis.
 ...
PMID:Management of allergic rhinitis: focus on intranasal agents. 257 39

Mast cell carboxypeptidase A has been isolated from the secretory granules of mouse peritoneal connective tissue mast cells (CTMC) and from a mouse Kirsten sarcoma virus-immortalized mast cell line (KiSV-MC), and a cDNA that encodes this exopeptidase has been cloned from a KiSV-MC-derived cDNA library. KiSV-MC-derived mast cell carboxypeptidase A was purified with a potato-derived carboxypeptidase-inhibitor affinity column and was found by analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be a Mr 36,000 protein. Secretory granule proteins from KiSV-MC and from mouse peritoneal CTMC were then resolved by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transblotted to polyvinylidine difluoride membranes. Identical aminoterminal amino acid sequences were obtained for the prominent Mr 36,000 protein present in the granules of both cell types. Based on the amino-terminal sequence, an oligonucleotide probe was synthesized and used to isolate a 1,470-base pair cDNA that encodes this mouse exopeptidase. The deduced amino acid sequence revealed that, after cleavage of a 15-amino acid hydrophobic signal peptide and a 94-amino acid activation peptide from a 417-amino acid preproenzyme, the mature mast cell carboxypeptidase A protein core has a predicted Mr of 35,780 and a high positive charge [Lys + Arg) - (Asp + Glu) = 17) at neutral pH. Although critical zinc-binding amino acids (His67, Glu70, His195), substrate-binding amino acids (Arg69, Asn142, Arg143, Tyr197, Asp255, Phe278), and cysteine residues that participate in intrachain disulfide bonds (Cys64-Cys77, Cys136-Cys159) of pancreatic carboxypeptidases were also present in mast cell carboxypeptidase A, the overall amino acid sequence identities for mouse mast cell carboxypeptidase A relative to rat pancreatic carboxypeptidases A1, A2, and B were only 43, 41, and 53%, respectively. RNA and DNA blot analyses revealed that mouse peritoneal CTMC, KiSV-MC, and bone marrow-derived mast cells all express a prominent 1.5-kilobase mast cell carboxypeptidase A mRNA which is transcribed from a single gene. We conclude that mouse mast cell carboxypeptidase A is a prominent secretory granule enzyme of mast cells of the CTMC subclass and represents a novel addition to the carboxypeptidase gene family.
 ...
PMID:Isolation and molecular cloning of mast cell carboxypeptidase A. A novel member of the carboxypeptidase gene family. 258 8


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