SUMMMARY1. Strips of longitudinal muscle can be obtained from guinea-pig ileum either retaining or free from Auerbach's plexus.2. The denervated strip is unresponsive to electrical stimulation by brief shocks, whether given singly or in trains; it also fails to respond to nicotine or dimethylphenylpiperazinium iodide (DMPP), and eserine causes no spasm.3. Denervated strips neither contain detectable acetylcholine ( < 0 4 ng/ mg), nor release it spont&neously (< 5 pg/mg/min) or in response to stimulation (< 31 pg/mg/min). The acetylcholine metabolism of the innervated strip is therefore that of the adherent Auerbach's plexus. Innervated strips had a mean acetylcholine content of 28 ng/mg, a mean resting output of 94 pg/mg/min and an output in response to stimulation at 10 c/s of 700-1200 pg/mg/min.4. By comparing the responses of innervated and denervated strips it was concluded that arecoline, methylfurmethide, a,8l-ethylal-y-trimethylammonium propanediol iodide (2268 F), muscarine, histamine, tremorine, oxytocin, and substance P, like acetylcholine, act primarily on the smooth muscle directly; and that angiotensin, barium, potassium, m-bromophenyl choline ether and 5-hydroxytryptamine have a progressively increasing proportionate effect on the nerve plexus. Nicotine and DMPP were inactive in the absence of the plexus.5. The longitudinal muscle with its accompanying plexus contains about one quarter of the acetylcholine of the whole ileum, and is responsible for about one fifth of the output to electrical stimulation.6. The volley output of acetylcholine by the innervated strip declines sharply as rate of stimulation increases. Output of acetylcholine was reduced by morphine and by cocaine, particularly when resting or when stimulated at low rates.

SUMMARY1. In mucosa-free preparations of the detrusor muscle electrical stimulation with 0.1 msec pulses has been utilized to reveal the non-cholinergic nature of most, if not all, of the post-ganglionic motor neurones in the guinea-pig bladder.2. The twitches elicited by 0.1 msec pulses were abolished by tetrodotoxin, but were not reduced by dimethyltubocurarine or by hexamethonium. Hexamethonium was nevertheless present in all the experiments in order to restrict acetylcholine action to 'muscarinic' receptors in the muscle fibres.3. There was little or no diminution in the twitches after prolonged exposure to atropine, 108-10-g/ml., although the twitch-matching dose of acetylcholine was raised 1000-2500 times. Hence, there was no anomalous refractoriness to atropine in these 'muscarinic' receptors.4. Despite massive atropinization, the recruitment of unoccupied transmitter-receptors by means of extra pulses remained unaffected.5. Eserine failed to potentiate the atropine-resistant twitches. 6. The twitches were not depressed by morphine. 7. Noradrenaline produced relaxation and twitch reduction. The twitches persisted after a +, adrenoceptor blockade with phentolamine + pronethalol and were unaffected by the monoamine oxidase and catecholamine-O-methyl transferase inhibitors, tranylcypromine and pyrogallol.8. Rapid contractions were elicited by 5-HT and by histamine but the twitches remained unaltered after antagonism of 5-HT by methysergide and of histamine by mepyramine.9. The twitches could be mimicked by injections of ATP, but after desensitization of the preparation to-ATP the response to -electrical stimulation remained unaltered. 11. The non-cholinergic nature of the post-ganglionic motor neurones was confirmed in the bladder of two other species, the cat and the rabbit.

SUMMARY1. Field stimulation of desheathed preparations of guinea-pig vas deferens, treated with a ganglion-blocking agent, has revealed the presence of two tetrodotoxin-susceptible components in the motor response, suggesting the existence of two sets of post-ganglionic motor nerve fibres of different excitability: one set responding maximally to pulses of 0 1-0 4 msec; the other, to pulses of 2 msec. No distinction could be made pharmacologically between the two components.2. Cooling potentiated that component in the twitch-responses which was due to stimulation of the more excitable fibres.3. The sensitivity of the longitudinal muscle to the motor action of noradrenaline was low and was subject to considerable animal variation. But normal responses to post-ganglionic field stimulation were elicited in noradrenaline-insensitive preparations, in which the twitches elicited by 5 pulses could not be matched with noradrenaline, even 100-125 ,tg/ml. 4. In some forty experiments, small doses of noradrenaline inhibited the twitch-responses evoked by either set of motor fibres. This inhibition differed from that produced by isoprenaline in two respects. Firstly, propranolol did not antagonize the noradrenaline inhibition, thus excluding an action on /J-adrenoceptors; and secondly, noradrenaline did not depress contractions elicited by muscarine or by 5-methylfurmethide.5. Phenoxybenzamine, 10-6 g/ml., produced a thousandfold reduction in the sensitivity of the muscle to the motor action of noradrenaline, without any decrease in the height of the twitches elicited by 0-1 or 1 msec pulses.6. The twitch-responses were not affected by combined a +15 adrenoceptor blockade with phentolamine and propranolol.7. Tyramine, amphetamine, tranylcypromine and prostaglandin E2 inhibited the twitches but potentiated the contractile effect of noradrenaline.N. AMBACHE AND M. ABOO ZAR 8. The twitch-responses and their inhibition by noradrenaline were present in preparations taken from reserpinized animals.9. Although the twitch-responses could be paralysed by bretylium or guanethidine, the foregoing results excluded adrenergic transmission at the motor endings. Cholinergic transmission was also excluded by negative findings with anticholinesterases, atropine, nicotine and (+ )-tubocurarine. 10. Motor transmission by histamine, 5-hydroxytryptamine, y-aminobutyric acid or ATP was also excluded.

SUMMARY1. The output of acetylcholine from the plexus of the guinea-pig ileum longitudinal strip has been used to study the mechanism of acetylcholine release. From the effects of hexamethonium and tetrodotoxin, it was inferred that 60 % of the normal resting output is due to propagated activity in the plexus, and 40 % to spontaneous release. Tetrodotoxin virtually abolishes the increase in output in response to electrical stimulation.2. Resting acetylcholine output is increased when the bathing medium is changed in the following ways:(a) sodium replacement by sucrose, trometamol or lithium; (b) addition of ouabain or p-hydroxymercuribenzoate (PHMB), or withdrawal of potassium;(c) the combination of PHMB and partial sodium replacement; (d) addition of potassium; this increase in output becomes greater in the absence of sodium.3. The resting output is virtually abolished by calcium withdrawal, and is restored by barium substitution for calcium. It is also reduced by raising the magnesium concentration.4. The enhanced resting output in response to sodium withdrawal also occurs in the absence of calcium.5. Cooling to 5°C greatly reduces both the resting output and the output in response to raised potassium concentration or to electrical stimulation.6. The increase in resting output due to potassium excess is slight up to 25 mm [K+]O, but increases thereafter with about the fourth power of the potassium concentration; it is resistant to tetrodotoxin.

SUMMARY1. Using field stimulation with short trains of pulses (< 10 per train), the post-ganglionic motor transmission in the mammalian vas deferens has been further analysed pharmacologically.2. In preparations taken from guinea-pigs, rats and rabbits the effects of the indirectly sympathomimetic drugs, tyramine and cocaine, could be explained entirely on the basis of the actions of released, endogenous noradrenaline.3. Tyramine produced a contraction in vasa taken from normal rats but not from normal guinea-pigs. The tyramine contraction was due to release of endogenous noradrenaline because it was not seen in preparations taken from reserpinized rats and because it was abolished in normal vasa by phenoxybenzamine or phentolamine, thus denying the supposed inaccessibility, to oc-blockers, of the motor ac-adrenoceptors activated by endogenous noradrenaline.4. Phenoxybenzamine or phentolamine failed to block post-ganglionic motor transmission in rat and in guinea-pig vasa.5. Tyramine strongly inhibited motor transmission in vasa taken from normal but not from reserpinized guinea-pigs.6. Tyramine produced inhibition of motor transmission in phenoxybenzamine-treated preparations taken from normal but not from reserpinized rats.7. Cocaine inhibited motor transmission in guinea-pig and in rat vasa. This effect was not due to a local anaesthetic or to a smooth-muscle depressant action because it did not occur in preparations taken from reserpinized animals.8. The inhibitory effect of tyramine or cocaine was not abolished by fl-adrenoceptor blockade with propranolol.

upon Tyne NE2 4HH1 The inhibitory transmission in isolated preparations of cavernosal smooth muscle from human penis has been studied. 2 Electrical field stimulation (EFS; 2-64 pulses/train, 0.8 ms pulse duration, 10Hz) evoked relaxation of preparations treated with guanethidine (5OpM). The EFS-evoked relaxations were atropine-resistant and tetrodotoxin-sensitive indicating their origin to be non-adrenergic, non-cholinergic (NANC) nerve stimulation. 3 EFS-evoked relaxation was attenuated dose-dependently by the nitric oxide (NO)-synthase inhibitor, L-NG-nitro arginine (L-NOARG; 0.3-100,aM) but not by D-N0-nitro arginine. The inhibitory effect of L-NOARG on transmission was antagonized by L-arginine (100pM), a NO precursor, but not by D-arginine.4 Incubation with methylene blue (10-50pM), a known inhibitor of guanylate cyclase activation by NO, caused a concentration-related inhibition of EFS-evoked relaxation. 5 It is concluded that NANC nerve-evoked relaxation of human cavernosal smooth muscle is mediated by NO or a NO-like substance.

The effect of the calcium channel blocker nifedipine on the motor transmission in isolated preparations of rat detrusor smooth muscle has been studied. Nifedipine blocked the major part (75 to 80%) of the contractile response to electrical field stimulation, while atropine only blocked 20 to 25%. In preparations pretreated with atropine, the response to electrical field stimulation was completely abolished by nifedipine. The converse was also true; in preparations pretreated with nifedipine the response was fully blocked by atropine. The nifedipine-resistant response was greatly potentiated by the anticholinesterase eserine. The blocking action of nifedipine on motor transmission was partially antagonised by raising Ca2(+)-concentration. Acetylcholine concentration-response curve was shifted to the right by nifedipine. It is concluded that the non-cholinergic motor neurotransmitter evokes contraction of the rat detrusor smooth muscle by activating external Ca2(+)-transport channels whereas the cholinergic contraction is mediated partly or wholly by alternative mechanisms.

The inhibitory post‐ganglionic transmission in the retractor penis of the ox resembles that of the dog and is not cholinergic or adrenergic. Acid extracts of this tissue have yielded an unidentified, labile, inhibitory substance which mimics the effect of its inhibitory nerves.