Interaction of aluminum ions with phosphoinositide metabolism in rat cerebral cortical membranes

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Life Sciences; (United States)

DOI:https://doi.org/10.1016/0024-3205(91)90137-Z· OSTI ID:5863008

Candura, S M; Castoldi, A F; Costa, L G ^[1]; Manzo, L ^[2]

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1. Univ. of Washington, Seattle (United States) Fondazione Clinica del Lavoro, Pavia (Italy)
2. Univ. of Pavia (Italy) Fondazione Clinica del Lavoro, Pavia (Italy)

Al, complexed with fluoride to form fluoroaluminate (AlF{sub 4}-), can activate the GTP-binding (G) proteins of the adenylate cyclase and retinal cyclic GMP phosphodiesterase systems. Since an involvement of G-proteins with cerebral phosphoinositide (PtdIns) metabolism has also been suggested, in this study the authors investigated the interaction of the stable GTP analogue GTP(S), Al salts and NaF with this system. In rat cerebral cortical membranes, GTP(S) dose-dependently stimulated ({sup 3}H)inositol phosphates (({sup 3}H)InsPs) accumulation. This effect was potentiated by carbachol and was partially prevented by the GTP-binding antagonist GDP(S), indicating that CNS muscarinic receptor activation is coupled to PtdIns hydrolysis via putative G-protein(s). GTP(S) stimulation was also inhibited by phorbol 12-myristate 13-acetate (PMA). Both Al salts and NaF mimicked the action of GTP(S) in stimulating PtdIns turnover. Their actions were highly synergistic. However, the stimulatory effects of AlCl{sub 3} and/or NaF were not potentiated by carbachol and were not inhibited by GDP(S) and PMA. In the nervous tissue, activation of PtdIns hydrolysis by Al may be mediated by activating a regulatory G-protein at a location distinct from the GTP-binding site or by a direct stimulation of phospholipase C.

• OSTI ID: 5863008
• Journal Information: Life Sciences; (United States), Vol. 49:17; ISSN 0024-3205
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ALUMINIUM
BIOLOGICAL EFFECTS
CYCLASES
ENZYME ACTIVITY
PHORBOL ESTERS
PHOSPHODIESTERASES
PHOSPHOLIPIDS
METABOLISM
CELL MEMBRANES
CEREBRAL CORTEX
DOSE-RESPONSE RELATIONSHIPS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
BODY
BRAIN
CARCINOGENS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CEREBRUM
ELEMENTS
ENZYMES
ESTERASES
ESTERS
HYDROGEN COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
LIPIDS
LYASES
MAMMALS
MEMBRANES
METALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PROTEINS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques