1 Strips of urethra taken from guinea-pigs contracted in response to acetylcholine, noradrenaline (via a-adrenoceptors) and 5-hydroxytryptamine, and were relaxed by adenosine triphosphate (ATP) if the tone was raised. Isoprenaline produced relaxation of bladder strips (via Padrenoceptors) whereas ATP caused contraction. 2 Atropine completely blocked all responses to acetylcholine; quinidine failed to block ATP responses selectively; methysergide blocked responses of the urethra but not the bladder to 5-hydroxytryptamine. 3 Spontaneous electrical activity was recorded with intracellular microelectrodes from all regions: in the urethra infrequent bursts of spikes occurred at 1-7 min intervals; regular spikes at 6-30/min were recorded from the detrusor muscle. In the bladder base, bursts of spikes were superimposed on the regular pattern. 4 Bursts of spikes in the urethra were initiated by noradrenaline, phenylephrine or acetylcholine and inhibited by ATP; regular spikes in the bladder were accelerated by acetylcholine or ATP and slowed by noradrenaline or isoprenaline. 5 The intrinsic electrical activity and pharmacological properties of the urethra therefore differ from those of the bladder. This may account for the different responses of the two regions in normal function.

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SUMMARY1. Supramaximal repetitive field stimulation with pulses of 50 /ts produced contraction of strips of bladder from rabbits and guinea-pigs. Atropine reduced responses at all frequencies to about 60 % and the contraction was poorly maintained.2. With the double sucrose-gap technique large excitatory junction potentials (e.j.p.s) were recorded with superimposed action potentials. These were not reduced by atropine or phentolamine.3. Substance P (SP) produced contraction and increased the frequency of spontaneous action potentials recorded with micro-electrodes from bladder strips. Vasoactive intestinal peptide (VIP) produced relaxation and slowed action potentials in rabbit but had no effect in guinea-pig; neurotensin, somatostatin and leu-enkephalin were without action in either species.4. When the tissue was kept in contact with SP, a second application after 10 min produced only a small contraction suggesting that SP receptors were densensitized. However, the electrical response to field stimulation was unchanged and the mechanical response was increased.5. Chymotrypsin reduced mechanical responses to SP but had no effect on responses to field stimulation. The SP analogue, D-Pro2, D-Phe7, D-Trp9-SP, had no effect on responses to SP or to field stimulation. 6. It is concluded that the bladder receives excitatory non-cholinergic innervation which is responsible for a large excitatory junction potential and contraction. Although SP can contract the detrusor muscle, it is unlikely that it is an excitatory transmitter or that any of the five peptides act as modulators of transmitter release.

SUMMARY1. The electrical and mechanical activity of strips of urethral smooth muscle from female ovariectomized rabbits were studied. Results were compared with strips from guinea-pigs, dogs and Tammar wallabies and with anaesthetized rabbits.2. From pressure recordings in intact animals and contractile responses of strips it was concluded that in the urethra of the rabbit both cholinergic and a-adrenergic receptors were excitatory.3. Urethral strips from rabbits and wallabies had continuous spontaneous mechanical activity that was reduced by pre-treatment with oestrogen. In dogs spontaneous activity was transient and in guinea-pigs was usually absent.4. The a-adrenergic agonist, phenylephrine, produced a dose-related contraction of urethral strips from all species. Pre-treatment with oestrogen produced no significant change in the rabbit and guinea-pig but increased sensitivity in the dog and wallaby.5. Electrical activity was recorded with micro-electrodes from smooth muscle cells of rabbit and guinea-pig urethra. In both species pre-treatment with oestrogen produced slight depolarization.6. In rabbits regular spike activity was recorded from all animals but there was a tendency for double spikes and reduced amplitude following oestrogen treatment. In guinea-pigs bursts of spikes occurred in control animals; after hormone treatment there was often incomplete recovery of spikes within the burst.7. The results indicate that oestrogens can influence the smooth muscle of the urethra by modifying both spontaneous activity and the responses to stimulation of a-adrenoceptors.

Although suramin reduces the excitatory effect of nerve activity in some species, it would produce little beneficial effect in the human hyperexcitable bladder as any inhibitory effect might be offset by the increase in spontaneous activity.