The Effect of Substance P on the Peristaltic Reflex of the Isolated Guinea‐pig Ileum

Abstract

The introduction of substance P into the lumen of the isolated guinea-pig ileum caused an increase in the number and amplitude of the peristaltic waves. In preparations in which the peristaltic reflex was abolished, by fatigue, by external or internal application of 5-hydroxytryptamine, or by lowering the temperature of the bath, the introduction of substance P into the lumen of the intestine restored peristalsis. This effect of substance P was absent in preparations in which the mucous membrane was removed. Hexamethonium abolished the effect of substance P on peristalsis. It is concluded that substance P acts on the afferent nervous elements of the peristaltic reflex arc, possibly on the sensory receptors.Substance P has been found in relatively high amounts in the intestine and brain of various animals, such as the monkey, horse, ox, pig, sheep, dog, cat, rabbit and man (v. Euler and Gaddum, 1931;Douglas, Feldberg, Paton and Schachter, 1951;Ehrenpreis and Pernow, 1952;Pernow, 1953). A factor having, qualitatively and quantitatively, the same properties as substance P has been shown to occur in the intestine of the cod and the dogfish and in cod brain (v. Euler and Ostlund, 1956). The retina of the cow has also been found to contain high amounts of substance P (Duner, v. Euler and Pernow, 1954).The exact physiological role of substance P is still unknown. A central stimulating effect of substance P has been shown by v. Euler and Pernow (1954), and evidence has been presented that substance P stimulates afferent fibres (Lembeck, 1957). In evaluating the action of substance P on the jejunum of the rabbit, Blair and Clark (1956) concluded that the stimulant action of substance P on intestinal motility is mediated through a very labile mechanism which could well have a trophic influence on the amplitude of spontaneous contractions. It is known that the peristalsis elicited by increased intraluminal pressure is augmented in the presence of substance P (Gernandt, 1942). In the present experiments the effect of substance P on the peristaltic reflex was studied, introducing the substance into the lumen of the guinea-pig ileum. MATERIALS AND METHODSFor recording the peristaltic activity a modification of the method of Trendelenburg (1917) was used, which has been described in detail in a previous paper (Beleslin and Varagid, 1958). By this method it was possible to introduce the drug into the lumen of the intestine and to wash it out. The peristaltic activity was recorded by means of Stephenson's float recorder which records volume changes (Stephenson, 1948).The peristaltic reflex was tested by raising the intraluminal pressure (varying from 30 to 50 mm. in different experiments) for 90 sec. at constant intervals.Several experiments were done with preparations from which the mucosa had been removed. For this purpose a loop of intestine was turned inside out by slipping it over a glass rod. The mucosa was gently scraped off using a piece of filter paper, and then the loop of intestine was returned to its normal position...

An improved method for studying the peristaltic reflex in the isolated colon

“…The role of the mucosa and submucosa in initiating the peristaltic reflex is still not clear. According to Builbring, Lin & Schofield (1958) and Beleslin & Varagic (1958), destruction of the mucosa abolishes the peristaltic reflex in the ileum, while contrary results have been reported by Ginzel (1959a, b). Diament, Kosterlitz & McKenzie (1961) found that spontaneous shedding of the superficial layers of the mucosa during an experiment does not decrease the efficiency of the peristaltic reflex.…”

An analysis of possible nervous mechanisms involved in the peristaltic reflex

“…Substances which stimulate sensory receptors in general, e.g. 5-HT, phenyl diguanide or S.R.KOTTEGODA 688 PERISTALTIC REFLEX substance P, when applied to the mucosa, stimulate peristalsis (Btilbring & Lin, 1958;Beleslin & Varagi6, 1958).…”

The Effect of Substance P on the Superior Cervical Ganglion of the Cat

“…Substance P. when acting on the outside of the isolated guinea-pig ileum, blocks the peristaltic reflex (Beleslin and Varagic, 1959). In previous work some evidence was obtained that this block of peristalsis might be at least partly produced by the action of substance P on the intestinal ganglia.…”

“…It is concluded that the potentiating effect of substance P on the response of the nictitating membrane to submaximal stimulation of the preganglionic sympathetic nerve is probably due to sensitization of acetylcholine receptors in the postsynaptic neurone. The present experiments do not explain how substance P potentiated the response to sympathomimetic amines.It has been shown that substance P may restore peristalsis when injected into the lumen of the isolated guinea-pig ileum in which the peristaltic reflex has been abolished by fatigue, by external or internal application of 5-hydroxytryptamine, or by lowering the temperature of the bath (Beleslin and Varagic, 1958). Substance P. when acting on the outside of the isolated guinea-pig ileum, blocks the peristaltic reflex (Beleslin and Varagic, 1959).…”

“…It has been shown that substance P may restore peristalsis when injected into the lumen of the isolated guinea-pig ileum in which the peristaltic reflex has been abolished by fatigue, by external or internal application of 5-hydroxytryptamine, or by lowering the temperature of the bath (Beleslin and Varagic, 1958). Substance P. when acting on the outside of the isolated guinea-pig ileum, blocks the peristaltic reflex (Beleslin and Varagic, 1959).…”