Opiate tolerance and dependence is associated with a decreased activity of GTPase in rat striatal membranes.
Life Sci
; 33 Suppl 1: 345-8, 1983.
Article
em En
| MEDLINE
| ID: mdl-6141494
ABSTRACT
In vitro addition of opiates to rat striatal membranes significantly stimulated a low Km GTPase activity. The opioid peptide (D-Ala2, Met5) enkephalinamide was ten folds more active than morphine to elicit the effect while the kappa agonist ethylketocyclazocine was almost inactive. Opiate stimulation was antagonized by naloxone, indicating that specific opiate receptors were involved. Moreover, the effect was stereospecific since levorphanol significantly increased the GTPase activity while its enantiomer dextrorphan was completely inactive, even at concentrations as high as 100 microM. On the other hand, opiates have been reported to inhibit striatal adenylate cyclase whose activity is dependent on GTP. Our data suggest therefore that stimulation of GTPase can be the mechanism by which opiates lower adenylate cyclase activity. This view is supported by the finding that in striatal membranes of rats made tolerant-dependent to morphine, GTPase activity was significantly decreased. Narcotic tolerance and dependence is in fact associated to hyperactivity of adenylate cyclase. It is concluded that GTPase could be the primary site on which opiates act to produce the acute or chronic effects on adenylate cyclase activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Monoéster Fosfórico Hidrolases
/
Corpo Estriado
/
GTP Fosfo-Hidrolases
/
Entorpecentes
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
1983
Tipo de documento:
Article