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Effect of morphine on synaptosomal Ca++ uptake
Abstract:
The effect of morphine on the uptake of 45Ca++ was studied in synaptosomes from mouse brain using two procedures, centrifugation and filtration. The addition of morphine (1.7 x 10(-7) or 3.4 x 10(-7) M) reduced 45CA++ uptake by either technique, although the basal 45Ca++ uptake by the filtration method was approximately 7-fold higher than that by the centrifugation procedure. Similar effects were obtained after acute morphine treatment with 10 mg/kg s.c. Previous naloxone in vitro treatment (1.9 x 10(-8) M) or in vivo administration (2 mg/kg s.c.) reversed the morphine inhibition of the 45Ca++ uptake. On the other hand, after the animal was rendered tolerant and dependent by morphine pellet implantation, an enhancement of the synaptosomal 45Ca++ uptake was observed. It is concluded that changes in Ca++ fluxes in synaptosomes observed after acute and chronic morphine treatment may be involved with morphine pharmacological action related with analgesia, tolerance and physical dependence.
Insights
Morphine affects calcium uptake in mouse brain synaptosomes. Acute morphine decreases uptake, while chronic use enhances it, suggesting calcium
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Calcium ions (Ca++) play a crucial role in neurotransmitter release and neuronal signaling.
- Morphine, an opioid analgesic, exerts its effects through complex interactions within the central nervous system.
- Synaptosomes, isolated nerve terminals, are valuable models for studying neuronal function and drug effects.
Purpose of the Study:
- To investigate the impact of morphine on calcium-45 (45Ca++) uptake in mouse brain synaptosomes.
- To explore the role of calcium fluxes in the development of morphine tolerance and physical dependence.
Main Methods:
- Utilized two distinct methods for measuring 45Ca++ uptake: centrifugation and filtration.
- Administered morphine acutely (subcutaneously) and chronically (pellet implantation) to mice.
- Investigated the effects of naloxone, an opioid antagonist, on morphine-induced changes in 45Ca++ uptake.
Main Results:
- Morphine addition in vitro and acute in vivo treatment significantly reduced 45Ca++ uptake in synaptosomes.
- Naloxone administration reversed the inhibitory effect of morphine on 45Ca++ uptake.
- Chronic morphine treatment led to an enhancement of 45Ca++ uptake in synaptosomes.
Conclusions:
- Changes in synaptosomal calcium fluxes are implicated in the pharmacological actions of morphine, including analgesia.
- Altered calcium handling in neurons may contribute to the development of morphine tolerance and physical dependence.
- These findings highlight the critical role of calcium homeostasis in opioid drug effects.