Activation of μ‐ and δ‐opioid receptors present on the same nerve terminals depresses transmitter release in the mouse hypogastric ganglion

1 The inhibitory actions of μ‐ and δ‐opioid receptor agonists on the strong, single fibre synaptic input to neurones contained in the mouse hypogastric ganglion have been examined. 2 The opioid agonists [ d ‐Ala 2 ,NMePhe 4 ,Gly‐ol 5 ]enkephalin (DAMGO, 10 n m ‐10 μ m ), morphine (10–30 μ m ), [ d ‐Ser 2 ,Leu 5 ,Thr 6 ]enkephalin (DSLET, 3 n m ‐1 μ m ), [ d ‐Pen 2 , d ‐Pen 5 ]enkephalin (DPDPE, 10 n m ‐10 μ m ), all depressed the single fibre, all‐or‐nothing, nicotinic, excitatory synaptic potential (e.p.s.p.) recorded in mouse hypogastric ganglion neurones. U50488H (0.3–1 μ m ) was without effect. 3 The effect of DSLET, but not that of DAMGO, was reversed by the δ‐opioid receptor‐selective antagonist, ICI 174864 (0.3 μ m ). Naloxone (0.3 μ m ) antagonized the effect of both DSLET and DAMGO. 4 The site of action of the μ‐ and δ‐receptor agonists was on the presynaptic terminals, since at the concentrations which depressed the e.p.s.p. these drugs did not affect the resting membrane potential or input resistance of the postganglionic neurone body, nor did they depress the postganglionic, nicotinic response to exogenously applied acetylcholine. 5 Quantal analysis further confirmed the presynaptic site of action; μ‐ and δ‐opioid receptor agonists decreased the mean number of quanta released per stimulus but did not reduce the mean amplitude of the quantal unit. 6 It was concluded that μ‐ and δ‐opioid receptors were located on the same presynaptic nerve terminals since, in the same neurones, μ‐ and δ‐opioid receptor agonists depressed the same single fibre inputs. 7 The potassium channel blockers barium and quinine, at concentrations known to block opioid‐activated somatic potassium conductances, reduced slightly but did not abolish the μ‐ and δ‐opioid receptor‐mediated inhibition of the e.p.s.p.