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

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Abstract
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.

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