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 μM. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 345-348 |
| Number of pages | 4 |
| Journal | Life Sciences |
| Volume | 33 |
| Issue number | SUPPL. 1 |
| DOIs | |
| Publication status | Published - 1983 |
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ASJC Scopus subject areas
- Pharmacology
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Opiate tolerance and dependence is associated with a decreased activity of GTPase in rat striatal membranes. / Parenti, Marco; Gazzotti, Giuliano; Tirone, Felice; Groppetti, Antonio.
In: Life Sciences, Vol. 33, No. SUPPL. 1, 1983, p. 345-348.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Opiate tolerance and dependence is associated with a decreased activity of GTPase in rat striatal membranes
AU - Parenti, Marco
AU - Gazzotti, Giuliano
AU - Tirone, Felice
AU - Groppetti, Antonio
PY - 1983
Y1 - 1983
N2 - 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 μM. 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.
AB - 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 μM. 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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UR - http://www.scopus.com/inward/citedby.url?scp=0021032899&partnerID=8YFLogxK
U2 - 10.1016/0024-3205(83)90513-1
DO - 10.1016/0024-3205(83)90513-1
M3 - Article
C2 - 6141494
AN - SCOPUS:0021032899
VL - 33
SP - 345
EP - 348
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - SUPPL. 1
ER -