Atropine-resistant longitudinal muscle spasms due to excitation of non-cholinergic neurones in Auerbach's plexus.

Abstract

1. In accordance with the dual histology of Auerbach's plexus (Dogiel, 1899; Hill, 1927) two types of neurone can be shown to be humorally active in plexus-containing preparations of longitudinal muscle from guinea-pig ileum, taken at measured distances up to 95 cm above the ileocaecal valve, when such preparations are stimulated electrically under different conditions.2. The rapid twitch, lasting 3-8 sec, which is elicited by single shocks of 0.1 or 0.2 msec pulse width, and the effect of 5-15 ng doses of acetylcholine which matched this twitch, were both extinguished equally effectively and completely by atropine sulphate (0.4-1 x 10(-8) g/ml.) or by hyoscine hydrobromide. This twitch-response is therefore caused by an excitation of cholinergic motor neurones of normal susceptibility to atropine. These are believed to be the Dogiel (1899) Type II cells of Auerbach's plexus, as suggested by Hill (1927).3. After extinction of the twitch by the invariably effective atropineblock, a second type of muscle response was revealed by tetanic stimulation with 1 sec trains of 50 pulses of the same voltage and of pulse width preferably 0.2 msec. The tetanic responses consisted of spasms of longer delay and duration (20-60 sec). These spasms could be matched by doses of acetylcholine of the order of 200 ng. However, if the atropine concentration was now raised to 10(-7), or even 10(-6) g/ml., the effect of 200-1000 ng of acetylcholine was abolished, but the tetanic spasms persisted without decrease in amplitude. In other experiments the height of the spasms remained constant as the concentration of atropine sulphate was raised from 10(-8) to 10(-6) g/ml. and was only slightly decreased by 10(-5) g/ml. Hence, these tetanic contractions are not due to a surmounting of the atropine-block by the increased release of acetylcholine following the 50 pulses.4. The tetanic spasms originate from excitation of non-cholinergic neurones, perhaps the associative Dogiel Type I cells of Auerbach's plexus (Hill, 1927), since the spasms were abolished reversibly by tetrodotoxin 2 x 10(-7) g/ml. and were absent from plexus-free, nicotine-insensitive preparations of the longitudinal muscle, both before and after atropinization.5. The tetanic spasms were not reduced by ganglion-block with paralysing doses of nicotine, with (+)-tubocurarine or with hexamethonium.6. The tetanic spasms are not mediated by a release of 5-hydroxytryptamine (5-HT) or of histamine, since they persisted in concentrations of methysergide and mepyramine adequate to block matching doses of histamine or 5-HT, or multiples thereof. Catecholamines were also excluded.7. The tetanic spasms are not mediated by a release of a prostaglandin, because they were not reduced by 0.5-2 x 10(-6) g/ml. of patulin (Ambache, 1957), which blocked the contractions evoked by matching doses of prostaglandins PGE(2) or PGF(2alpha); even after this block, PGE(2) still potentiated subsequent tetanic responses.8. The tetanic spasms were reduced or virtually abolished by strychnine in concentrations which did not depress the twitch.