The isolated vas deferens of the guinea-pig contracted when stimulated transmurally with parallel wire electrodes. These contractions persisted in concentrations of hexamethonium, pentolinium, nicotine and mecamylamine which at the same time abolished the responses to hypogastric nerve stimulation. Procaine and lignocaine in local anaesthetic concentrations abolished the responses to transmural stimulation but potentiated the contractions produced by added noradrenaline. Guanethidine and bretylium in concentrations specific for adrenergic neurone blockade abolished the contractions due to transmural stimulation without impairing the responses of the muscle to added noradrenaline or acetylcholine. In contrast, high concentrations of the adrenergic-blocking agents phentolamine and dihydroergotamine were needed to block the contractions due to transmural stimulation; these concentrations also blocked the response to added noradrenaline but simultaneously reduced the responses to added acetylcholine or potassium chloride. Preparations from guinea-pigs previously treated with reserpine at first responded normally to transmural stimulation; thereafter the contractions diminished progressively but were never abolished. Hyoscine and atropine produced a small decrease in the response to transmural stimulation when present in concentrations up to 1x10(-5) and a larger decrease only in concentrations of 1x10(-4) or greater. Hemicholinium produced a small decrease of the contractions due to transmural stimulation in concentrations up to 1x10(-4); concentrations of 5x10(-4) present for 1 hr produced only a slightly greater reduction in response. These experiments show that when the guinea-pig vas deferens is removed without the hypogastric nerve and stimulated transmurally by the method described, contractions are produced mainly by excitation of postganglionic adrenergic nerves.
These results indicate that human detrusor smooth muscle cells in culture express M3 muscarinic receptors which are linked to phosphoinositide hydrolysis.
SUMMARY1. The post-ganglionic nerve fibres to the vas deferens of the guinea-pig and rat were interrupted in vivo by stripping one vas deferens of its serous coat; the other vas deferens was left intact as a control.2. Four to eight days later the stripped vas deferens did not contract in response to electrical transmural stimulation in vitro at 01 msec pulse duration. Pulses of 1.0 msec duration produced small contractions which were not abolished by local anaesthetic or adrenergic neurone-blocking drugs.3. Log dose-response curves to noradrenaline were, for stripped vasa deferentia, to the left of those for control vasa. The increase in sensitivity to noradrenaline at 8 days was about sixteenfold for rat vasa and about tenfold for guinea-pig vasa. Tyramine did not contract stripped vasa from guinea-pigs or rats.4. The noradrenaline and adrenaline content of guinea-pig and rat vasa was greatly reduced or abolished 8 days after the stripping operation.5. Fluorescent nerve terminals were usually absent when transverse sections of stripped vasa were examined by fluorescence microscopy after treatment by the formaldehyde condensation method for demonstrating catecholamines.6. It is concluded that post-ganglionic sympathetic denervation is achieved by stripping the vas deferens in vivo of its serous coat and mesenteric attachments.
The adrenergic α‐receptor blocking activity of 4‐(2‐dimethylaminoethoxy)‐5‐isopropyl‐2‐methylphenyl acetate, thymoxamine, was quantitatively investigated on the vas deferens of the guinea‐pig and on arterial strips from guinea‐pigs, rabbits, cats and dogs. The blockade fulfilled the established criteria for competitive antagonism of noradrenaline. On these various tissues the pA2 was about 7.0; thymoxamine was more potent than piperoxan and less potent than dihydroergotamine. There was no evidence of β‐receptor or 5‐hydroxytryptamine receptor blocking activity. Against histamine as the agonist on the guinea‐pig ileum, thymoxamine was a competitive antagonist with a pA2 of about 6.5.
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