1. A study was made on the mechanisms by which enkephalins inhibit synaptic transmission at calyx-type presynaptic terminals in the ciliary ganglion of chick embryos at stages 39-40. 2. Excitatory postsynaptic currents (EPSCs) were recorded by nystatin-perforated patch clamp at low [Ca2+](o) and high [Mg2+](o). [Leu5]enkephalin (L-ENK, 1-10 μM) reduced the quantal content (m) without changing the quantal size (q). This effect was antagonized by naloxone (1 μM). Similar results were observed under conventional whole-cell clamp of the postsynaptic neuron. 3. A specific agonist of the μ-opioid receptor, [D-Ala2,M-Me-Phe4,Gly5]enkephalin-ol (DAMGO) reduced m without changing q. A specific agonist of the δ-opioid receptor, [D-Pen2,D-Pen5]enkephalin (DPDPE) also reduced m without changing q. 4. Both L-ENK and [Met5]enkephalin (M-ENK) reduced the stimulus-dependent increment of the intraterminal Ca2+ concentration (Δ[Ca2+](t)) without affecting the decay time constant of the intraterminal Ca2+ concentration and basal Ca2+ level. This effect was antagonized by naloxone. DAMGO reduced Δ[Ca2+](t) more effectively than DPDPE. 5. When extracellular Ca2+ was replaced by Ba2+, the stimulus-dependent increment of the intraterminal Ba2+ concentration (Δ[Ba2+](t)) was also reduced by L-ENK or DAMGO. 6. L-ENK reduced Δ[Ca2+](t) even in the presence of 4-aminopyridine (4-AP), which blocks the transient K+ conductance during the falling phase of the presynaptic action potential. When N-type Ca2+ channels were blocked by ω-conotoxin GVIA (ω-CgTx(GVIA)), the Δ[Ca2+](t) was no longer sensitive to L-ENK and DAMGO. 7. It is suggested that enkephalins reduce the transmitter release through presynaptic opioid receptors. The μ-opioid receptor may suppress presynaptic Ca2+ influx by selectively inhibiting N-type Ca2+ channels.
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