A B S T R A C T The possibility that the autonomic nervous system may influence the function of intestinal mucosa was investigated by assessing the effect of acetyl choline on ion transport in human intestine. Isolated pieces of stripped ileal mucosa were mounted in Perspex flux-chambers and bathed in isotonic glucose Ringer's solution. Acetyl choline caused a rise in mean potential difference (8.8-12.3 mV, P < 0.002) and short circuit current (287.7-417.2 A'A -cm-2, P < 0.01) (n = 12), observable at a concentration of 0.01 mM and maximal at 0.1 mM. This effect was enhanced by neostigmine and blocked by atropine. Isotopic flux determinations revealed a change from a small mean net Cl absorption (+ 0.58) to a net Cl secretion (-4.3 Aeq-cmf'-h P < 0.001) due predominantly to an increase in the serosal to mucosal unidirectional flux of Cl (10.63-14.35 ueq. cm . h-' P < 0.05) and a smaller reduction in the mucosal to serosal flux (11.22 to 10.02 /Aeq cm-' h' P < 0.05). Unidirectional and net Na transport was unaffected. A similar electrical and ion transport response was observed in a single study of two pieces of jejunal mucosa. In the absence of glucose net chloride secretion was produced and again an insignificant effect on net sodium transport was noted. Acetyl choline did not provoke a sustained effect on mucosal cyclic adenine nucleotide levels although a short-lived cyclic adenine nucleotide response was seen in some tissues 20-30 s after drug addition.These studies demonstrate that acetyl choline does influence human intestinal ion transport by stimulating chloride secretion and suggest a possible mechanism by A preliminary report of this work was presented at the British Society of Gastroenterology, Southampton, April 1975 and at the European Society for Clinical Investigation, Rotterdam, April, 1975. Received for publication 20 August 1975 and in revised formn 13 May 1976. which the parasympathetic nervous system could be concerned in the control of ion transport. INTRODUCTION It has long been thought that the autonomic nervous system may influence intestinal absorption and secretion. Sympathetic denervation in the dog and the cat caused an intestinal secretion which was blocked by atropine(1) and the spontaneous secretion of Thirty-Vella loops of dog ileum was similarly prevented by atropine (2).More recently Caren and co-workers (3) showed that the secretion provoked by tactile stimulation in such isolated loops was inhibited by atropine and hexamethonium. Pilocarpine (4) and eserine (5) caused intestinal secretion and bethanechol, a cholinergic agent, was shown to induce a net secretion of chloride in dog jejunum (6). In view of these suggestive pieces of evidence the present investigations were undertaken to examine in more detail the influence of acetyl choline on human intestinal ion transport. The results indicate that acetyl choline does influence ion transport in vitro and suggest a possible mechanism by which the parasympathetic nervous system could be involved in the control of intestina...
sUMMARY The transport of sodium and chloride across human jejunal and ileal mucosa was studied using an in vitro technique. Specimens of mucosa removed at operation were stripped of muscle coats, mounted in specially designed Perspex flux chambers and bathed in warmed oxygenated and stirred buffer solutions.Evidence was obtained for the active transport of sodium in both jejunum and ileum and of chloride in the ileum. Sodium absorption was enhanced by glucose in both regions of the gut but net chloride transport was unaffected. Glucose had a greater effect on sodium transport in the ileum than the jejunum.The electrical potential difference and resistance was greater and undirectional ion fluxes smaller in jejunal than ileal mucosa.Many of these results with human intestine are similar to results reported with in vitro animal intestine. Apparent discrepancies between the behaviour in vivo of human intestine and in vitro of animal intestine are thus likely to be due predominantly to technical rather than species differences.Much current information about mechanisms of intestinal electrolyte transport rests on the results of in vitro investigations using animal intestine.Human intestinal ion transport on the other hand has been studied mainly by in vivo techniques and relatively few in vitro investigations have been undertaken. Such discrepant observations as the failure of glucose to enhance sodium absorption in vivo in human ileum (Fordtran et al., 1968) but not in vitro in the rabbit ileum (Schultz and Zalusky, 1964b) and the failure to demonstrate bicarbonate absorption in vitro in rabbit jejunum (Fromm, 1973), while in vivo in man it clearly occurs (Fordtran et al., 1968), could be due to species differences or to technical variations. The present human in vitro studies were undertaken for comparison with in vitro animal and in vivo human intestinal behaviour. Methods
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