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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated the role of mast cell degranulation in the mediation of hypoxic pulmonary vasoconstriction, and its prevention by intravenous cromolyn sodium. In the present investigation, we studied the modification of the hypoxic pulmonary vascular response by aerosolized cromolyn sodium. In seven conscious sheep on two separate days, pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output were measured for the calculation of pulmonary vascular resistance (Rpv) along with arterial oxygen tension (Pao2) during room air breathing and breathing a hypoxic gas mixture (13% O2-87% N2), without and with cromolyn sodium administration. Cromolyn sodium (20 mg X kg-1) was administered as an aerosol before and during 13% O2 breathing. The sheep had comparable degrees of hypoxia during low oxygen breathing on both days (mean PaO2: 43 and 46 mmHg). Breathing hypoxic gas mixture caused pulmonary vasoconstriction, with increases in mean Rpv of 89% (p less than 0.05). Aerosolized cromolyn sodium blunted the hypoxic pulmonary vascular response; mean Rpv increased by 27% (p less than 0.05), which was significantly different from the increase during hypoxia without cromolyn sodium treatment (p less than 0.05). We conclude that aerosolized cromolyn sodium (a mast cell membrane stabilizing agent) modifies hypoxic pulmonary vasoconstriction; however, unlike the intravenous form, aerosolized cromolyn sodium (at the dosage used) offers a partial protection.
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PMID:Modification of hypoxic pulmonary vasoconstriction by aerosolized cromolyn sodium. 308

We investigated the effect of cromolyn sodium, a mast cell stabilizing agent, on the pulmonary vascular response to alveolar hypoxia in six chronically instrumented lambs aged 9 to 11 days. Each lamb was instrumented on day 6 or 7 for measurements of systemic arterial, pulmonary arterial and left atrial pressures, and pulmonary blood flow. The animals were allowed to recover from surgery at least 3 days before they were studied. Each animal was studied twice, once with a cromolyn sodium infusion and once with a normal saline infusion (placebo). These paired experiments were separated by 24 h. Physiologic measurements were made during a 1-min predose control period, after an 8-min drug or placebo infusion, and after a 15-min period of alveolar hypoxia. Cromolyn sodium infusion alone did not affect baseline cardiovascular variables. Alveolar hypoxia following placebo infusion produced an increase in pulmonary arterial pressure and pulmonary vascular resistance; these responses were blocked in the animals given cromolyn sodium prior to induction of hypoxia. These results show that cromolyn sodium blocks the pulmonary vascular response to hypoxia and provide indirect evidence that mast cell degranulation, with subsequent release of vasoactive agents, mediates the pulmonary vascular response to hypoxia in newborn lambs.
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PMID:Cromolyn sodium decreases the pulmonary vascular response to alveolar hypoxia in lambs. 309 74

Serum pepsinogen concentrations rose more rapidly and to higher levels in adult sheep infected with Ostertagia circumcincta and treated orally with the mast cell stabilising agent sodium cromoglycate than they did in adult sheep infected with the parasite which remained untreated. Sodium cromoglycate did not affect the serum pepsinogen concentrations or abomasal pH in uninfected sheep.
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PMID:Effect of sodium cromoglycate on the response to Ostertagia circumcincta in adult sheep. 312 Feb 62

Ascaris suum antigen effects on mean airflow resistance (RL) and bronchial arterial blood flow (Qbr) were studied in allergic anesthetized sheep with documented airway responses. Qbr was measured with electromagnetic flow probes, and supplemental O2 prevented antigen-induced hypoxemia. Aerosol challenge with this specific antigen increased RL and Qbr significantly. Cromolyn sodium aerosol pretreatment prevented antigen-induced increases in RL but not in Qbr. Intravenous cromolyn, however, prevented increases in Qbr and RL, suggesting a role for mast cell degranulation in both bronchomotor and bronchovascular responses to antigen. Antigen-induced increases in Qbr were not solely attributable to histamine release. Indomethacin pretreatment attenuated the antigen-induced increase in Qbr, thus suggesting that vasodilator cyclooxygenase products contribute to the vascular response. Antigen challenge significantly decreased Qbr after indomethacin and metiamide pretreatment, which suggests that vasoconstrictor substances released after antigen exposure also modulate Qbr; however, released vasodilators overshadow vasoconstrictor effects. Thus antigen challenge affects Qbr by locally releasing histamine and vasodilator prostaglandins as well as vasoconstrictor substances. These effects were independent of antigen-induced changes in systemic and pulmonary hemodynamics.
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PMID:Modification of bronchial blood flow during allergic airway responses. 313 32

Hypoxia-induced pulmonary hypertension may be mediated by leukotrienes. Pulmonary mast cells produce leukotrienes, histamine and prostaglandin D2, and degranulate in response to hypoxia. Cromolyn sodium, a mast cell membrane stabilizing agent, may prevent hypoxia-induced mast cell degranulation. To investigate the role of mast cell products in hypoxia-induced pulmonary hypertension, we studied the haemodynamic responses to alveolar hypoxia before and during an intravenous infusion of 3-5 mg/min per kg of cromolyn sodium in 6 chronically instrumented, spontaneously breathing lambs. Since there are age-dependent differences in the response of the pulmonary circulation to some mast cell products, we studied the effects of cromolyn sodium on hypoxia-induced pulmonary hypertension in newborn (4-7 days) and young lambs (15-18 days). During alveolar hypoxia, mean pulmonary arterial pressure increased by 68% (P less than 0.05) and 59% (P less than 0.05) in the newborn and young lambs, respectively. With alveolar hypoxia during cromolyn sodium infusion, mean pulmonary arterial pressure increased by 71% (P less than 0.05) and 42% (P less than 0.05) in the newborn and young lambs, respectively. Cromolyn sodium did blunt the hypoxia-induced release of histamine into the circulation. Because hypoxia-induced pulmonary hypertension was not inhibited by cromolyn sodium in either age group, mast cell products are not important mediators of hypoxia-induced pulmonary hypertension.
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PMID:Cromolyn sodium does not prevent hypoxia-induced pulmonary hypertension in newborn and young lambs. 314 68

In allergic bronchospasm inhaled allergen interacts with specific IgE antibody on the surface of mast cells, inducing the release of mediators, particularly histamine and leukotrienes, which induce bronchoconstriction. Disodium cromoglycate, previously considered to be predominantly a mast cell stabilizing agent, is effective prophylactically in inhibition of early and late phase asthmatic reactions. However, the microenvironment of the airways contains many cell types and the precise role of mast cells is not clear. Lymphocytes, alveolar macrophages, eosinophils, platelets, and neutrophils possess low affinity surface receptors for IgE and can respond to allergen, releasing mediators that have diverse functions. These observations compound the problem of which mediator(s) is most important in pathogenesis of asthma. Moreover, mast cell products modulate the functions of many cells, and thus whether mast cells act directly or indirectly on bronchial smooth muscle requires clarification. Neuropeptides activate or modulate mast cells, and together with evidence of the close association of mast cells and nerves, these observations provide exciting new directions for investigation. Evidence that mast cells from different sites are heterogeneous in their response to stimuli and antiallergic drugs and differ in mediator production and function amplifies the problems identified above. In summary, the role of mast cells in bronchoconstriction is complex and systematic analysis of interactions between mast cells and other cells of the airways is essential.
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PMID:The role of the mast cell in allergic bronchospasm. 355 49

Sodium cromoglycate (SCG) blocks histamine release from sensitized mast cells challenged by antigen in vitro. Yet, not all the observed effects of SCG in vivo can be explained by this mechanism alone. Rapidly-adapting or "irritant" receptors (RAR) are thought to mediate reflex bronchoconstriction. Others have proposed that SCG may desensitize these receptors to histamine. We administered aerosols of histamine (100 micrograms/ml given for 3 min) before and after SCG (20 mg/ml aerosol for 5 min) to adult, mongrel dogs. SCG did not reduce the increase in tracheal pressure or RAR activity in response to histamine challenge. We also administered aerosols of Ascaris suum antigen (7 min) to dogs which had shown a positive skin reaction to subepidermal injection of this antigen. SCG attenuated both the increase in tracheal pressure and RAR nerve activity in response to the antigen challenge. These findings suggest that SCG does not affect the activity of the RAR or decrease the tracheal pressure in response to histamine challenge in an anesthetized dog, whereas SCG is effective in decreasing the response of both these parameters to antigen challenge when given prophylactically presumably by stabilizing the mast cell membrane.
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PMID:Activity of rapidly-adapting receptors to histamine and antigen challenge before and after sodium cromoglycate. 392 60

The actions of two mast cell stabilising agents, FPL 52694 and disodium cromoglycate and the Ca2+ channel antagonist verapamil on acid secretion by the rat isolated stomach have been studied. FPL 52694 (1-5 mM) in the serosal medium stimulated acid secretion. This was antagonised by prostaglandin E2 but not by atropine, metiamide, propranolol or tetrodotoxin. FPL 52694 (1-5 mM) in the mucosal medium had an inhibitory effect on basal acid secretion and that stimulated by pentagastrin and histamine. The inhibition reversed only slowly after removal of FPL 52694. Disodium cromoglycate and serosal application of verapamil had no significant effects on acid output. Removal of calcium from the bathing solutions and mucosal verapamil inhibited basal secretion. Topically applied, FPL 52694 is a potent inhibitor of acid secretion in vitro. This effect may involve an action upon the availability of calcium to the tissue. The stimulatory effects of serosal FPL 52694 are discussed in relation to previous in vivo findings.
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PMID:The action of two mast cell stabilising agents and verapamil on rat gastric acid secretion in vitro. 393 83

Disodium cromoglycate has recently been approved for ophthalmic treatment of certain types of conjunctivitis in the United States. This mast cell inhibitor is effective in the treatment of vernal keratoconjunctivitis, allergic conjunctivitis, chronic conjunctivitis, and giant papillary conjunctivitis, especially when a history of atopic disorders or moderately low blood IgE levels are present. This literature review provides a foundation for understanding the balance between the therapeutic efficacy, clinical benefits and side effects in treating IgE-mediated conjunctivitis with disodium cromoglycate.
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PMID:Ophthalmic disodium cromoglycate. 393 47

Calcium permeability of basophil and mast cell membranes is stimulated on allergen binding to its specific membrane-bound IgE. This entry of Ca2+ ions into the cell triggers the degranulation and secretion process. Disodium cromoglycate (cromolyn DSCG), the disodium salt of 1,3-bis(-2-carboxychromon-5-yloxy)-2-hydroxypropane, inhibits the degranulation and release of anaphylactic mediators, and has found wide application in the treatment of allergic bronchial asthma. Accumulated evidence indicates that this inhibition takes place by blocking the calcium uptake. To localize its site of action, the drug has been covalently conjugated to fluorescent polyacrylamide and polyglutaraldehyde beads (0.7 and 0.2 microns in diameter, respectively). We show here that these drug-bead conjugates (DBC) do prevent the drug penetrating into the cell without reducing its ability to inhibit histamine release (Table 1). Furthermore, we show a specific Ca2+-dependent binding of the DBC to the membranes of rat peritoneal mast cells (RPMC) and basophils.
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PMID:A binding site on mast cells and basophils for the anti-allergic drug cromolyn. 615 90


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