Effects of some drugs on the responses of the rat isolated, innervated urinary bladder to indirect electrical stimulation.

1. The effects of some drugs known to inhibit transmission in the superior cervical ganglion and at the neuromuscular junction were investigated on the cholinergic nerve-smooth muscle junction, using the rat isolated innervated urinary bladder preparation.2. HC-3 and Win 4981 inhibited the indirectly evoked contractions; the block was typically slow in onset, depended on the rate of stimulation and was partially reversed by choline. The moderate coincident inhibition of acetylcholine-responses disappeared after washing the tissue, while the block of the neuronally evoked contractions persisted.3. Morphine, methylpentynol carbamate, chloral hydrate and strychnine inhibited indirectly evoked contractions without inhibiting the responses to acetylcholine. Paraldehyde inhibited both types of response.4. Hexamethonium, mecamylamine and tubocurarine had no effect on either type of response. Tetraethylammonium augmented both types of response; the augmentation due to lower concentration was followed by a moderate block of the neuronally evoked contractions.5. Small concentrations of procaine markedly inhibited responses to acetylcholine and produced a partial block of the neuronally evoked contractions.6. None of the drugs affected conduction in the isolated phrenic nerve.7. All the drugs other than paraldehyde and procaine appeared to act at the nerve terminals. The results are generally consistent with the view that HC-3 and Win 4981 act by limiting transport of choline across nerve membrane and that the other drugs act by inhibiting the release of acetylcholine. A reduction in sensitivity of the effector cell membrane may account, wholly or in part, for the action of paraldehyde and procaine.