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Department of Pharmacology, School of Medicine, University of Pittsburgh, PA 15261.

1. Repetitive stimulation (10-20 Hz, 0.5-5 s duration) of the preganglionic nerves to ganglia on the surface of the urinary bladder of the cat produced a prolonged inhibition (duration, 30-65 s) of the postganglionic action potentials, elicited by low-frequency stimulation (0.25-1 Hz) of another preganglionic nerve to the same ganglion. 2. Intra-arterial administration of naloxone, an opiate antagonist (20-50 micrograms/kg), reduced the magnitude and duration of this heterosynaptic inhibition and also blocked the depression of ganglionic transmission elicited by the intra-arterial administration of leucine-enkephalin (0.1-10 micrograms/kg). 3. Naloxone did not alter adrenergic inhibition elicited by repetitive stimulation of the hypogastric nerve or exogenous noradrenaline. Naloxone did not alter the postganglionic firing elicited by single stimuli or trains of low-frequency (1-3 Hz) stimuli to the preganglionic nerves. 4. Heterosynaptic inhibition was not altered by the administration of antagonists for alpha-adrenergic (dihydroergotamine, prazosin, yohimbine), muscarinic (atropine), purinergic (theophylline) or GABAergic (picrotoxin) receptors. 5. A delta-selective opiate receptor agonist, DSLET (D-Ser2-leucine-enkephalin-Thr), inhibited parasympathetic ganglionic transmission in low doses (mean threshold dose, 0.02 microgram/kg, I.A.), whereas a mu-opiate receptor agonist, morphine sulphate, produced only a small depression in larger doses (mean threshold dose, 100 micrograms/kg, I.A.). Ethylketocyclazocine, which has an affinity for kappa-receptors did not alter transmission in relatively large doses (1 mg/kg, I.A.). 6. These findings coupled with previous immunocytochemical demonstrations of leucine-enkephalin-like immunoreactivity in preganglionic nerve terminals in bladder ganglia suggest that opioid peptides released endogenously from preganglionic nerves are involved in delta-receptor-mediated inhibitory mechanisms at cholinergic synapses in bladder ganglia.

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