Maitotoxin: Effects on calcium channels, phosphoinositide breakdown, and arachidonate release in pheochromocytoma PC12 cells

Journal Article · Thu Feb 01 00:00:00 EST 1990 · Molecular Pharmacology; (USA)

OSTI ID:7191576

Choi, O H; Padgett, W L; Nishizawa, Y; Gusovsky, F; Yasumoto, T; Daly, J W ^[1]

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1. National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD (USA)

Maitotoxin (MTX) increases formation of (3H)inositol phosphates from phosphoinositides and release of (3H)arachidonic acid from phospholipids in pheochromocytoma PC12 cells. Formation of (3H)inositol phosphates is detected within 1 min of incubation even with concentrations as low as 0.3 ng/ml (90 pm) MTX, whereas release of (3H)arachidonic acid is not detected until 20 min even with concentrations as high as 1 ng/ml (300 pm) MTX. Stimulation of arachidonic acid release can be detected at 0.03 ng/ml (9 pm) MTX, whereas 0.1 ng/ml (30 pm) MTX is the threshold for detection of phosphoinositide breakdown. Organic and inorganic calcium channel blockers, except Cd2+ and a high concentration of Mn2+, have no effect on MTX-elicited phosphoinositide breakdown, whereas inorganic blockers (e.g., Co2+, Mn2+, Cd2+), but not organic blockers (nifedipine, verapamil, diltiazem), inhibit MTX-stimulated arachidonic acid release. All calcium channel blockers, however, inhibited MTX-elicited influx of 45Ca2+ and the MTX-elicited increase in internal Ca2+ measured with fura-2 was markedly reduced by nifedipine. MTX-elicited phosphoinositide breakdown and arachidonic acid release are abolished or reduced, respectively, in the absence of extracellular calcium plus chelating agent. The calcium ionophore A23187 has little or no effect alone but, in combination with MTX, A23187 inhibits MTX-elicited phosphoinositide breakdown and enhances arachidonic acid release, the latter even in the absence of extracellular calcium. The results suggest that different sites and/or mechanisms are involved in stimulation of calcium influx, breakdown of phosphoinositides, and release of arachidonic acid by MTX.

• OSTI ID: 7191576
• Journal Information: Molecular Pharmacology; (USA), Vol. 37:2; ISSN 0026-895X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ARACHIDONIC ACID
SECRETION
CALCIUM COMPOUNDS
MEMBRANE TRANSPORT
PHOSPHOLIPIDS
METABOLISM
TOXINS
BIOLOGICAL EFFECTS
ADRENAL GLANDS
CALCIUM 45
LIPASES
PHOSPHATES
PORINS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CARBOXYLESTERASES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
ENDOCRINE GLANDS
ENZYMES
ESTERASES
ESTERS
EVEN-ODD NUCLEI
GLANDS
HYDROGEN COMPOUNDS
HYDROLASES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LIPIDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MONOCARBOXYLIC ACIDS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHOSPHORUS COMPOUNDS
PROTEINS
RADIOISOTOPES
RODENTS
TOXIC MATERIALS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques