Morphine withdrawal in vitro: potentiation of agonist-dependent polyphosphoinositide breakdown.
Naloxone (10(-5) -10(-9) M) significantly increased the K+ (30 mM)-induced release of [3H[noradrenaline when it was applied to cortical slices taken from morphine-dependent rats but did not change the release of transmitter when applied to slices prepared from non-dependent animals. Therefore, this preparation was considered suitable to study withdrawal-related events and was used to monitor the agonist-induced changes of phospholipase C activity in the withdrawal state. Noradrenaline (1-100 microM) and carbachol (50-500 microM), when applied to cortical slices preincubated with [3H]inositol or with [32P]orthophosphate, dose dependently increased the formation of labeled inositol phosphates or of phosphatidic acid. This confirmed that noradrenaline and carbachol increase phospholipase C activity. This increase was significantly enhanced by naloxone (10(-6) M) when the slices were taken from dependent animals. The results now reported show for the first time in mammalian tissues that opioid withdrawal is associated with changes of phosphoinositide metabolism.
Pellegrini-Giampietro
D E
DE
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Ruggiero
M
M
Giannelli
S
S
Chiarugi
V P
VP
Moroni
F
F
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D009270:Naloxone; D011189:Potassium Chloride; D009020:Morphine; D002217:Carbachol; D010738:Type C Phospholipases; D009638:Norepinephrine