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

The principal pathological features of asthma, including tracheobronchial smooth muscle contraction and mast cell mediator synthesis and release, are calcium-dependent processes. Calcium plays an integral role in transmitting signals at the cell surface to the enzymatic machinery of the cell interior; its role as the agent for "excitation-contraction coupling" of airway smooth muscle and for "stimulus-secretion coupling" of mast cells is reviewed. A rise in intracellular calcium ion concentration triggers cellular activation. In smooth muscle, calcium bound to calmodulin stimulates the myosin light chain kinase which is important in the regulation of actin-myosin interaction. In mast cells, calcium may bind to calmodulin or to a calmodulinlike regulatory protein, and it also stimulates enzymes important in the synthesis of newly generated mediators including prostaglandins and leukotrienes. The regulatory role of cyclic AMP in both cell systems is discussed, especially as it pertains to calcium metabolism. By interfering with transmembrane calcium fluxes, the calcium channel blocking drugs have the potential for significantly modifying bronchoconstriction and airway inflammation in asthma and related bronchospastic disorders. Some of the in vitro studies of calcium channel blockers in these two cell systems are reviewed. Finally a speculation about the role of abnormal sensitivity to calcium in airway smooth muscle as a potential cause of airway hyperreactivity is entertained.
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PMID:Role of calcium in airway smooth muscle contraction and mast cell secretion. 608 60

Although the critical role of systemic inflammatory edema in the development of multiple organ failure in patients with massive burns has been fully recognized, the precise mechanisms responsible for the accumulation of blood fluid and proteins in tissues remote from the burn wound are poorly understood. The aim of this study was to test the hypothesis that circulating factors released during thermal injury cause microvascular leakage by triggering endothelial cell contraction and barrier dysfunction. A third-degree scald burn was induced in rats on the dorsal skin covering 25% total body surface area. The microcirculation and transvascular flux of albumin were observed in the rat mesentery using intravital fluorescence microscopy. The direct effect of circulating factors on microvascular barrier function was assessed by measuring the apparent permeability coefficient of albumin in isolated rat mesenteric venules during perfusion of plasma freshly withdrawn from burned rats. The in vivo study showed that the transvenular flux of albumin was significantly increased over a 6-h period with a maximal response seen at 3 h postburn. Importantly, perfusion of noninjured venules with burn plasma induced a time-dependent increase in albumin permeability. Pharmacological inhibition of protein kinase C, Src tyrosine kinases, or mast cell activation did not significantly affect the hyperpermeability response; however, blockage of myosin light chain phosphorylation with the myosin light chain kinase inhibitor ML-7 greatly attenuated the burn-induced increase in venular permeability in a dose-related pattern. The results support a role for endogenous circulating factors in microvascular leakage during burns. Myosin light chain phosphorylation-dependent endothelial contractile response may serve as an end-point effector leading to microvascular barrier dysfunction.
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PMID:Myosin light chain kinase-dependent microvascular hyperpermeability in thermal injury. 1450 51

Colorectal hyperalgesia has been supposed to be one of the key pathophysiological roles in irritable bowel syndrome (IBS). Recent animal models have demonstrated that neonatal maternal deprivation (stress memory) or repetitive rectal distension (pain memory) in neonatal animal triggers long-term hypersensitivity to rectal distension, indicating that negative events including abuse or maternal separation in childhood may play a crucial role on development of IBS. Several molecules such as corticotropin-releasing factor, serotonin, nerve growth factor, myosin light chain kinase, chemical mediators from mast cell, substance P and calcitonin gene-related peptide released from transient receptor potential vanilloid receptor 1 (TRPV1)-positive primary afferent nerves have been proved to induce visceral hyperalgesia. Novel drugs based on these findings have been developed.
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PMID:[Visceral hypersensitivity]. 1689 10