Electrical and motor activity of the surgically-altered gastroduodenal junction of the dog.
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Biomedical subjects
Publications and source records attributed to P Bass.
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The relationship of the surface properties of a group of anionic surfactants to their effects on intestinal water transport was studied. Dose-response inhibition of water transport in everted hamster jejunal segments was obtained with two long chain detergents (sodium dodecyl sulfate and dioctyl sodium sulfocuccinate), a fatty acid (ricinoleate), and dihydroxy bile salts (deoxycholate, chenodeoxycholate, and taurodeoxycholate), whereas no activity was seen with trihydroxy (cholate, glycocholate, and taurocholate) and tri-keto (dehydrocholate) bile salts. The relative effects on water transport were paralleled by their abilities to lyse the erythrocyte, a membrane model. These two biological effects were related to the surface properties of the agents, as determined by critical micelle concentration and surface tension reduction. We further characterized the action of deoxycholate on hamster small intestine, in vivo. Net water secretion was accompanied by increases in permeability of the mucosa to inulin, dextran, and albumin. These secretory and permeability changes were accompanied by both biochemical and histological alterations: exfoliation (DNA release), membrane effects (sucrase release), and shortened villi. Electron microscopy revealed extensive alteration of the brush border membrane with a decrease in binding of lanthanum and the development of permeability to tracer in villus tip cells. In contrast, taurocholate, which did not alter water transport, did not affect intestinal permeability or the brush border membrane. We believe that the surface properties of anionic surfactants cause changes in absorptive cell membranes which result in intestinal secretion.
Circular muscle contractile activity of the antrum and duodenum and gastric emptying of a liquid test meal were investigated in unanesthetized dogs in which the gastroduodenal junction (GDJ) was altered (Heineke-Mikulicz pyloroplasty). After pyloroplasty, antralization (antral-like contractions occurring in the first portion of the duodenum) was observed during the digestive state. Antralization replaced the normal periods of inhibition that separate periods of duodenal contractions during the interdigestive burst. Bethanechol (0.1 mg/kg sc) and metoclopramide (2.0 mg/kg iv) were capable of stimulating interdigestive contractile activity in the altered GDJ. Pentagastrin (1.0 mug/min iv) produced a differential stimulation on the antrum without appreciably affecting duodenal contractile activity. Pyloroplasty also enhanced the emptying of a 300-ml citrate-fat liquid test meal. An intact hypomuscular segment between the antrum and duodenum is important for normal coordinated contractile activity between the antrum and the duodenum and for the normal gastric emptying of liquids.
The mechanism of hydroxy fatty acid-induced secretion was investigated in perfused hamster small intestine in vivo. Sodium ricinoleate at an 8-mM concentration resulted in not only secretion of water and sodium, but an increase in intestinal clearance of inulin and a 16,000 mol wt dextran as well. A concentration of ricinoleate (2 mM) which did not affect water transport, however, did not alter intestinal permeability. Ricinoleate-induced intestinal secretion was also accompanied by increased mucosal cell exfoliation as measured by the appearance of DNA in the perfusate and by apparent injury to epithelial cell membranes as judged by measurement of sucrase activity and phospholipid in cell-free aliquots of luminal fluid. Light and electron microscopic studies demonstrated substantial mucosal architectural changes with 8 mM ricinoleate with villus shortening and injury to epithelial cells at the villus tips. In contrast, cholera enterotoxin caused marked secretion of sodium and water, presumably by a cyclic AMP mechanism, but did not alter inulin clearance or enhance DNA or sucrase appearance in the lumen. These studies suggest that at least a component of ricinoleate-induced intestinal secretion is related to structural alterations of the mucosa.
Intraduodenal infusion of ricinoleic acid and iv bolus injection of the C-terminal octapeptide of cholecystokinin produce markedly similar alterations in the digestive contractile patterns of the GI tract of the unanesthetized dog. The brief, initial stimulation of contractile activity in the proximal small intestine following both procedures is mediated through a cholinergic mechanism. The stimulatory response is followed by an inhibition of digestive contractile activity of unknown origin. These observations suggest that possibility that the GI hormone, cholecystokinin, may mediate the intestinal motor response evoked by infusion of ricinoleic acid directly into the proximal small intestine.
Oleic and ricinoleic acids or their trans isomers, elaidic and ricinelaidic acids, were administered intraduodenally and evaluated for their effects on the digestive motor activity of the canine small and large bowel. Four dogs of mixed breed were implanted with duodenal cannulas and extraluminal strain gage transducers along the circular axis of the proximal and mid-jejunum, terminal ileum, and proximal colon. After feeding 200 g of canned dog food to induce continuous contractile activil of isotonic saline was given into the duodenum as a single bolus infusion and recordings were made for a 1-hr period. A 30-ml volume of saline served as control. Administration of each cis fatty acid produced an initial stimulation in jejunal areas of about a 2-min duration followed by a post-stimulatory inhibition. Both the initial stimulation and post-stimulatory inhibition were greater for ricinoleic acid than for oleic acid. Minimal or no effects were produced in ileal or colonic areas. In contrast, the trans isomers produced little or no effect on either the small or large bowel. Alterations in the digestive contractile patterns produced by oral administration of 10 ml of oleic, ricinoleic acid or their respective triglycerides were also tested. Triolein had no effects. Ricinoleic acid and castor oil poduced a brief initial stimulation followed by polonged inhibition of small bowel motor activity. Both cathartics had a mild laxative effect. Digestive motor patterns returned to control approximately 45 min after oleic acid. There was no indication at any time of an initiation of continuous contractile activity after ricinoleic acid or castor oil which could justify the use of the terms irritant of stimulant to describe their actions.
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Castor oil and magnesium sulfate were studied for their effects on gastrointestinal contractile activity in vivo. Ricinoleic acid, the active ingredient in castor oil, magnesium sulfate and mannitol were studied and compared for their effects on net water and electrolyte absorption in vitro. Extraluminal strain gauge transducers were implanted in dogs and used to monitor the circular smooth muscle activity of the antrum, duodenum, ileum and colon after water, castor oil or a 30 percent solution of magnesium sulfate. Substances were tested during the interdigestive (fasted) and digestive (fed) states. Decreases in total activity were found for both cathartics in the antrum and ileum. Further analysis revealed that decreases in the ileum occurred primarily by a decrease in contractile rate, whereas antral decreases could be attributed primarily to a decrease in force per contraction. Proximal colonic activity tended to decrease after laxatives and feeding. The effects of ricinoleic acid, isotonic and hypertonic solutions of magnesium sulfate and mannitol on net water and electrolyte absorption were tested on everted segments of hamster jejunum. Sodium ricinoleate (2.0 mM) reduced net water transport by 48 percent (P smaller than .01). Magnesium sulfate, like mannitol, only reduced net water absorption when present as a component of a hypertonic mucosal solution. The results suggest that both inhibition of water absorption and reduced circular smooth muscle activity may be important factors in castor oil- and magnesium sulfate-induced catharsis.
Ricinoleic acid and several structurally related compounds were tested for their effects on the smooth muscle contractions of the coaxially stimulated guinea-pig ileum, the spontaneously contracting rabbit jejunum, 90 mM potassium depolarized guinea-pig taenia coli and rat colon. In concentrations of 1.25 X 10(-5) to 4 X 10(-4) M, ricinoleate produced a dose-dependent depression of the stimulated guinea-pig ileum. This action was not produced by matching concentrations of oleate, elaidate, linoleate, 12-hydroxystearic acid, 10(9)-hydroxystearate, the methyl ester of ricinoleic acid or the trans isomer, recinelaidate. The alcohol derivative, ricinoleyl alcohol, was active and, although the depression produced by it took longer to maximize, the dose-response curves for ricinoleate and ricinoleyl alcohol on this tissue were almost superimposable. Ricinoleate showed the same qualitative and quantitative effects on the spontaneously contracting rabbit jejunum, but several differences were noted on the depolarized preparations. Ricinoleate-induced depression of depolarized smooth muscle was much slower in onset and required about 10 times higher concentrations to achieve equivalent responses. The results show that ricinoleic acid, the active ingredient in castor oil, is not a stimulant or irritant to isolated intestinal smooth muscle.
Ricinoleic acid, the active component of castor oil, and related fatty acids were studied to determine their relative inhibitory effects on water and electrolyte absorption using everted hamster jejunal and ileal segments. Differences were found between hydroxylated and nonhydroxylated congeners as well as between cis and trans geometric isomers. At a mucosal concentration of 2.0 mM, the unsaturated fatty acids had the following rank order of potency on inhibition of water absorption: ricionoleate greater than or equal to ricinelaidate- greater than equal to linoleate greater than oleate greater than linelaidate greater than elaidate. Ricinoleyl alcohol was effective at 2.0 mM but the methyl ester of ricinoleic acid was ineffective at this concentration. Among a series of saturated fatty acids including palmitate, stearate, a mixture of 9- and 10-hydroxystearate, and 12-hydroxystearate, only the last compound had any inhibitory effect on water absorption. The results define those portions of the ricinoleic acid molecule required for its effect on water and electrolyte absorption and suggest that classification of this cathartic as an "irritant" or "stimulant" should be re-evlauated.
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The antral-duodenal contractile relationship was studied in control, after parietal cell vagotomy and truncal vagotomy conditions using extraluminal strain gage transducers. All conditions were investigated under interdigestive and digestive states and after insulin, bethanechol and histamine. After parietal cell vagotomy, there was minimal alteration of the antral-duodenal relationship in both the interdigestive and digestive states. The number and amplitude of contractions on both the antrum and duodenum (as reflected by a motility index) were not changed from control by the various stimulants. The one exception was that histamine markedly stimulated the duodenal contractile activity. In the truncal vagotomy condition, there was a total disruption of the antral-duodenal relationship in the interdigestive and digestive states. There was a significant decrease in the number and amplitude of contractions occurring on the antrum during the interdigestive and after insulin stimulation. Food was ineffective in stimulating the antrum in 2 of 3 dogs. In contrast, motor activity of the duodenum was minimally influenced by truncal vagotomy. In conclusion, parietal cell vagotomy has minimal disruptive effects on the antralduodenal relationship while truncal vagotomy reduces antral contractile activity.
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