Cyclic nucleotide regulation of inositol lipid metabolism in rat cerebral cortex

Conference · Thu May 01 00:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7169750

Nicchitta, C V; Williamson, J R

The authors have investigated the effects of compounds known to elevate cAMP levels and/or activate the cAMP dependent protein kinase on resting and stimulated inositol lipid metabolism in rat cortical slices and synaptosomes. In (/sup 3/H)-myo-inositol-labeled brain slices, carbamylcholine-stimulated accumulation of (/sup 3/H)-myo-inositol 1-phosphate (IP/sub 1/) was decreased 50% by forskolin (150..mu..M) isobutylmethylxantihine (IBMX) (1mM), 8-bromo cAMP (5mM) or 8-(4-chlorophenylthio) cAMP (5mM). In studies with synaptosomes, the incorporation of (/sup 32/Pi) into phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP/sub 2/) and phosphatidic acid (PA) was also reduced in the presence of forskolin or the cAMP phosphodiesterase inhibitors IBMX and RO20-1724 (+/-)-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone. In the presence of maximally effective concentrations of these agents, steady state PIP levels were reduced by 50% and PIP/sub 2/ and PA levels by 40%. The effects of these compounds on (/sup 32/Pi) labeling of the phosphoinositides and PA are consistent with an inhibition of flux through the inositide cycle, presumably through the action of cAMP. Such an inhibition may account for the reduction in carbamylcholine sensitive IP/sub 1/ accumulation observed in brain slices. These studies indicate that in rat brain, ..beta..-adrenergic stimulation may be involved in modulating the activity of muscarinic cholinergic agonists. This regulation appears to be at the level of inositol lipid metabolism.

• Research Organization: Univ. of Pennsylvania School of Medicine, Philadelphia
• OSTI ID: 7169750
• Report Number(s): CONF-8606151-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMP
ANIMALS
AROMATICS
AZAARENES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
BRAIN
CARBOHYDRATES
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
ESTERS
HETEROCYCLIC COMPOUNDS
INHIBITION
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIPIDS
MAMMALS
METABOLISM
MONOSACCHARIDES
NERVES
NERVOUS SYSTEM
NUCLEI
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHOLIPIDS
PHOSPHORUS 32
PHOSPHORUS COMPOUNDS
PHOSPHORUS ISOTOPES
PURINES
RADIOISOTOPES
RATS
RODENTS
SACCHARIDES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
XANTHINES