Evidence for the release of two atropine-resistant spasmogens from Auerbach's plexus

1. Two atropine-resistant response-components of nervous origin have been detected in plexus-containing preparations of the longitudinal muscle from the guinea-pig ileum, by alternate field stimulation with equal numbers of pulses at 50 Hz (response A) and at 5 Hz (response B). With trains of ten or more pulses, response A is always larger than B; the ratio of A/B (1.2-21.3) is subject to animal variation.2. Both responses are abolished by tetrodotoxin and are absent from plexus-free preparations.3. Neither response is reduced by ganglion-block with (+)-tubocurarine, dimethyltubocurarine or hexamethonium, or by ganglion-paralysing doses of nicotine; the contribution of excited preganglionic endings to these responses is therefore negligible.4. Neither response is due to a release of histamine, 5-hydroxytryptamine (5-HT) or prostaglandins, since both A and B persist in the presence of mepyramine, methysergide and the prostaglandin-antagonist SC-19220 (1-acetyl-2(8-chloro-10,11-dihydrodibenz [b,f] [1,4]oxazepine-10-carbonyl) hydrazine).5. The two response-components are affected differentially by a number of drugs.6. Histamine, 0.1 mug/ml., reduces response A to the level of B; this selective inhibition of the histamine-sensitive component in A is specifically antagonized by nicotine, 1-2.5 x 10(-5) g/ml.7. 5-HT, 0.1 mug/ml., and strychnine, 20-40 mug/ml., also reduce response A to the level of B, but these selective inhibitions are not antagonized by nicotine.8. Diphenhydramine, 10 mug/ml., produces equality of the two responses by depressing A and potentiating B.9. The inhibitory effects of the foregoing drugs are not due to catecholamine release, since they persist after alpha + beta adrenoceptor blockade with phentolamine and pronethalol, and after previous reserpinization of the guinea-pigs.10. In atropinized plexus-containing preparations of the longitudinal muscle from the guinea-pig descending colon, the responses elicited at 50 Hz and at 5 Hz are virtually equal and both appear to be of Type B since they are not inhibited by histamine, 5-HT or strychnine; diphenhydramine produces strong contractions.