Lysosomotropic amines modulate neutrophil calcium homeostasis. 1988

B Styrt, and M S Klempner
Department of Medicine, Michigan State University, East Lansing 48824.

Lysosomotropic amines can raise the acidic internal pH of the neutrophil lysosome and inhibit neutrophil function. Because pH and calcium regulation are intimately connected in various types of excitable cells, we studied the effects of several lysosomotropic weak bases on neutrophil calcium homeostasis. Base-treated cells had normal to minimally elevated resting cytosol free calcium, but weak bases produced significant release of calcium from organelles when this release was directly measured in permeabilized cells, even after depletion of inositol-triphosphate-sensitive stores. Collapse of transmembrane pH gradients with monensin similarly released organelle calcium. The initial cytosol calcium response to f-met-leu-phe was enhanced by some of the lysosomotropic amines but the calcium rise was more transient in base-treated cells than in control samples. These findings suggest that existence of an acidic intracellular compartment, such as the lysosome, is important to normal calcium homeostasis in the neutrophil and that pH sensitivity and inositol triphosphate sensitivity may define two pools of releasable organelle calcium. The effect of pH perturbation on calcium homeostasis may partially account for the inhibition of neutrophil function by lysosomotropic amines.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D008744 Methylamines Derivatives of methylamine (the structural formula CH3NH2).
D008985 Monensin An antiprotozoal agent produced by Streptomyces cinnamonensis. It exerts its effect during the development of first-generation trophozoites into first-generation schizonts within the intestinal epithelial cells. It does not interfere with hosts' development of acquired immunity to the majority of coccidial species. Monensin is a sodium and proton selective ionophore and is widely used as such in biochemical studies. Coban,Monensin Monosodium Salt,Monensin Sodium,Monensin-A-Sodium Complex,Rumensin,Monensin A Sodium Complex
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D011433 Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs. Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002981 Clindamycin An antibacterial agent that is a semisynthetic analog of LINCOMYCIN. 7-Chloro-7-deoxylincomycin,Chlolincocin,Chlorlincocin,Cleocin,Clindamycin Hydrochloride,Clindamycin Monohydrochloride,Clindamycin Monohydrochloride, Monohydrate,Dalacin C,7 Chloro 7 deoxylincomycin,Hydrochloride, Clindamycin,Monohydrate Clindamycin Monohydrochloride,Monohydrochloride, Clindamycin,Monohydrochloride, Monohydrate Clindamycin
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
D005456 Fluorescent Dyes Chemicals that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. Flourescent Agent,Fluorescent Dye,Fluorescent Probe,Fluorescent Probes,Fluorochrome,Fluorochromes,Fluorogenic Substrates,Fluorescence Agents,Fluorescent Agents,Fluorogenic Substrate,Agents, Fluorescence,Agents, Fluorescent,Dyes, Fluorescent,Probes, Fluorescent,Substrates, Fluorogenic

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