Opiates inhibit acetylcholine release from Torpedo nerve terminals by blocking Ca2+ influx

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Torpedo electric organ provides a model for cholinergic neurotransmission.
• Opiate receptors have been identified in various nervous systems.
• The role of presynaptic receptors in modulating neurotransmitter release is crucial.

Purpose of the Study:

• To investigate the mechanism of morphine's inhibition of acetylcholine release.
• To determine if presynaptic opiate receptors are present in cholinergic neurons.
• To elucidate the role of calcium influx in opiate-mediated inhibition.

Main Methods:

• Electrophysiology and neurotransmitter release assays using Torpedo synaptosomes.
• Measurement of 45Ca2+ influx into nerve terminals.
• Pharmacological manipulation with morphine and naloxone.
• Use of K+ depolarization and Ca2+ ionophore (A23187) to stimulate release.

Main Results:

• Morphine inhibited Ca2+-dependent acetylcholine release from K+-depolarized synaptosomes.
• This inhibition was blocked by the opiate antagonist naloxone.
• Morphine reduced 45Ca2+ influx into depolarized synaptosomes in a dose-dependent manner.
• Morphine did not inhibit acetylcholine release when Ca2+ influx was bypassed using a Ca2+ ionophore.

Conclusions:

• Torpedo electric organ cholinergic neurons possess presynaptic opiate receptors.
• Opiate activation inhibits acetylcholine release by blocking voltage-dependent Ca2+ channels.
• This mechanism underlies opiate modulation of neurotransmitter release.