Phencyclidine (PCP)-like inhibition of N-methyl-D-aspartate-evoked striatal acetylcholine release, /sup 3/H-TCP binding and synaptosomal dopamine uptake by metaphit, a proposed PCP receptor acylator

Journal Article · Mon Dec 14 00:00:00 EST 1987 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(87)90279-7· OSTI ID:5298731

Snell, L D; Johnson, K M; Yi, S J; Lessor, R A; Rice, K C; Jacobson, A E

The phencyclidine (PCP) receptor acylator, metaphit, has been reported to act as a PCP antagonist. Recent electrophysiological and behavioral assessments of metaphit action have revealed, however, that this compound can also act as a PCP-like agonist. The present study examined the effects of metaphit on the inhibition of N-methyl-D-aspartate (NMDA)-induced /sup 3/H-acetylcholine (ACh) release, /sup 3/H-TCP binding and synaptosomal /sup 3/H-dopamine (DA) uptake in the rat striatum. Preincubation of striatal slices for 10 min in the presence of metaphit, followed by a prolonged washout, produced a concentration-dependent inhibition of the ACh release evoked by 300 ..mu..M NMDA. At high concentrations, preincubation with PCP also resulted in inhibition of this measure. However, this could be reduced by extending the washout period, a procedure which had no effect on the inhibition produced by metaphit. At 10..mu..M, metaphit resulted in a 53% reduction in NMDA-evoked ACh release while PCP had no effect under identical conditions. Preincubation of slices in 10 ..mu..M PCP and metaphit reduced the metaphit inhibition by 62%. The effects of PCP and metaphit, alone or in combination, on NMDA-induced ACh release were paralleled by a loss of /sup 3/H-TCP binding sites in striatal tissue incubated under identical conditions suggesting that metaphit exerts long-lasting agonist-like actions on PCP receptors coupled to NMDA receptors. 27 references, 3 figures, 1 table.

• Research Organization: Univ. of Texas Medical Branch, Galveston (USA)
• OSTI ID: 5298731
• Journal Information: Life Sci.; (United States), Vol. 41:24
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
SECRETION
DOPAMINE
UPTAKE
PHOSPHORIC ACID ESTERS
BIOCHEMICAL REACTION KINETICS
PIPERIDINES
RECEPTORS
ASPARTIC ACID
EXPERIMENTAL DATA
INHIBITION
NERVES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
AMINO ACIDS
AMMONIUM COMPOUNDS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
CARBOXYLIC ACIDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
DATA
DRUGS
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INFORMATION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PARASYMPATHOMIMETICS
PHENOLS
POLYPHENOLS
PROTEINS
PYRIDINES
QUATERNARY COMPOUNDS
REACTION KINETICS
SYMPATHOMIMETICS
550201* - Biochemistry- Tracer Techniques