Abstract
Oxytocin release from neurophypophysial terminals is particularly sensitive to inhibition by the micro-opioid receptor agonist, DAMGO. Because the R-type component of the neurophypophysial terminal Ca2+ current (ICa) mediates exclusively oxytocin release, we hypothesised that micro-opioids could preferentially inhibit oxytocin release by blocking this channel subtype. Whole-terminal recordings showed that DAMGO and the R-type selective blocker SNX-482 inhibit a similar ICa component. Measurements of [Ca2+]i levels and oxytocin release confirmed that the effects of DAMGO and SNX-482 are not additive. Finally, isolation of the R-type component and its associated rise in [Ca2+]i and oxytocin release allowed us to demonstrate the selective inhibition by DAMGO of this channel subtype. Thus, micro-opioid agonists modulate specifically oxytocin release in neurophypophysial terminals by selectively targeting R-type Ca2+ channels. Modulation of Ca2+ channel subtypes could be a general mechanism for drugs of abuse to regulate the release of specific neurotransmitters at central nervous system synapses.
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