Ca2+-mediated generation of inositol 1,4,5-triphosphate and inositol 1,3,4,5-tetrakisphosphate in pancreatic islets. Studies with K+, glucose, and carbamylcholine
The role of Ca2+ in the generation of inositol phosphates was investigated using rat pancreatic islets after steady state labeling with myo-(2-/sup 3/H)inositol. Depolarizing K+ concentrations (24 mM) evoked early (2 s) increases in inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and inositol 1,3,4,5-tetrakisphosphate (Ins-1,3,4,5-P4) as measured by high performance anion-exchange chromatography. The increase in Ins-1,4,5-P3 was transient and was followed by a more pronounced rise in Ins-1,3,4-P3. These effects were dependent on the presence of extracellular Ca2+ but were not secondary to release of either neurotransmitters or metabolites of arachidonic acid. K+ also promoted the breakdown of phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2) and of the other phosphoinositides. Glucose (16.7 mM) was less marked in its effects but still promoted rapid increases in Ins-1,3,4,5-P4 (2 s) and Ins-1,4,5-P3 (10 s) and a slower rise in Ins-1,3,4-P3 (30 s). The levels of all three metabolites rose steadily over 10 min stimulation. These responses to glucose could be largely, although not entirely, inhibited by depletion of extracellular Ca2+ or by Ca2+ channel blockade with verapamil (20 microM). Carbamylcholine (0.5 mM) was the most potent stimulus used evoking early rises in Ins-1,4,5-P3 and Ins-1,3,4,5-P4 (2 s) followed by Ins-1,3,4-P3 (10 s), effects which were only partially dependent on extracellular Ca2+. The results suggest that a Ca2+-mediated PtdIns-4,5-P2 hydrolysis accounts for most of the Ins-1,4,5-P3 generated in response to glucose but not carbamylcholine.
- Research Organization:
- Univ. of Geneva, Switzerland
- OSTI ID:
- 6594192
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 8
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CALCIUM COMPOUNDS
BIOLOGICAL FUNCTIONS
GLUCOSE
BIOCHEMICAL REACTION KINETICS
PHOSPHOLIPIDS
METABOLISM
POTASSIUM COMPOUNDS
CATIONS
CHOLINE
IN VITRO
INOSITOL
ION EXCHANGE CHROMATOGRAPHY
METABOLITES
PANCREAS
RATS
TRITIUM COMPOUNDS
ALCOHOLS
ALDEHYDES
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
BODY
CARBOHYDRATES
CHARGED PARTICLES
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DRUGS
ENDOCRINE GLANDS
ESTERS
FUNCTIONS
GLANDS
HEXOSES
HYDROXY COMPOUNDS
INOSITOLS
IONS
KINETICS
LABELLED COMPOUNDS
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
QUATERNARY COMPOUNDS
REACTION KINETICS
RODENTS
SACCHARIDES
SEPARATION PROCESSES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques