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The effects of capsaicin upon electrogenic ion transport in rat descending colon.

Preparations of rat descending colon mucosa have been used to record changes in short circuit current (SCC) under voltage clamp conditions. When added to the basolateral compartment capsaicin (8-methyl-N-vanillyl-6-nonenamide, 0.1-3 microM) caused an initial transient increase in SCC, followed by a more prolonged reduction in SCC, that lasted for 20-30 min. Repeated applications of 3 microM capsaicin caused desensitisation of the initial secretory response. The antisecretory effects (i.e. reduction in SCC from the original baseline) remained, although they were significantly reduced. In some preparations described as "non-responders", 3 microM capsaicin did not elicit a secretory response. No desensitization of the remaining antisecretory responses was observed in these tissues; in fact these reductions in SCC were consistently larger than those from tissues which responded with a secretory response. Tetrodotoxin (100 nM), hexamethonium (10 microM), and yohimbine (50 microM) had no significant effect upon either secretory or antisecretory responses. Ruthenium red (10 microM) abolished the secretory response to 3 microM capsaicin, but had no effect upon the antisecretory responses. Pretreatment of the tissues with 1 microM substance P (SP) resulted in significant desensitisation to the peptide and abolished the secretory response to 3 microM capsaicin. The antisecretory responses remained, and were significantly larger compared with responses from control tissues.

Animals↗

Apical membrane properties and amiloride binding kinetics of the human descending colon.

The apical membrane properties of the isolated human descending colon were characterized by use of current fluctuation analysis methods and microelectrode techniques. The Na+ channel blocker amiloride was used to evaluate apical membrane conductance and the transepithelial short-circuit current (Isc). Amiloride significantly reduced Isc and increased the membrane resistance ratio. At submaximal doses of amiloride in the mucosal bathing solution, fluctuation analysis of the Isc revealed a Lorentzian component in the power-density spectra. The dose-response relationship between amiloride and current noise parameters was consistent with a two-state mechanism of blocker interaction with the channel. The on and off rate constants for the blocker-receptor reactions, the single-channel currents, and the Na+ channel density were estimated and were similar to those from Na+ channels from other so-called tight epithelia. In addition, these studies revealed an amiloride-insensitive conductance in the apical membrane in parallel to the amiloride-blockable Na+ channels. This conductance may be due to potassium ions. If so, the apical membrane properties of the human descending colon may closely resemble those of the rabbit descending colon and rat distal colon.

Adult↗

Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by transforming growth factor beta and angiotensin II.

BACKGROUND: Absorption of water and Na+ in descending colonic crypts is dependent on the barrier function of the surrounding myofibroblastic pericryptal sheath. Here the effects of high and low Na+ diets and exposure to whole body ionising radiation on the growth and activation of the descending colonic pericryptal myofibroblasts are evaluated. In addition the effect of a post-irradiation treatment with the angiotensin converting enzyme inhibitor Captopril was investigated. METHODS: The levels of Angiotensin II type 1 receptor (AT1), ACE, collagen type IV, transforming growth factor-beta type 1 receptor (TGF-betaR1), OB cadherin and alpha-smooth muscle actin in both descending colon and caecum were evaluated, using immunocytochemistry and confocal microscopy, in rats fed on high and low Na+ diets (LS). These parameters were also determined during 3 months post-irradiation with 8Gy from a 60Co source in the presence and absence of the angiotensin converting enzyme inhibitor, Captopril. RESULTS: Increases in AT1 receptor (135.6% +/- 18.3, P < 0.001); ACE (70.1% +/- 13.1, P < 0.001); collagen type IV (49.6% +/- 15.3, P < 0.001); TGF-+/-beta1 receptors (291.0% +/- 26.5, P < 0.001); OB-cadherin (26.3% +/- 13.8, P < 0.05) and alpha-smooth muscle actin (82.5% +/- 12.4, P < 0.001) were observed in the pericryptal myofibroblasts of the descending colon after LS diet. There are also increases in AT1 receptor and TGF-beta1 receptor, smooth muscle actin and collagen type IV after irradiation. Captopril reduced all these effects of irradiation on the pericryptal sheath and also decreased the amount of collagen and smooth muscle actin in control rats (P < 0.001). CONCLUSIONS: These results demonstrate an activation of descending colonic myofibroblasts to trophic stimuli, or irradiation, which can be attenuated by Captopril, indicative of local trophic control by angiotensin II and TGF-beta release.

Actins↗

The effects of distension of the stomach and the descending colon on phasic coronary blood flow in the anesthetized pig.

Previous studies in anesthetized animals showed that distension of the stomach or the descending colon primarily caused decreases in mean coronary blood flow. Whether these responses occurred during systole or diastole was not investigated. The present work was planned to study the primary effects of the distension of the two viscera on phasic coronary blood flow in the anesthetized pig. In ten animals, the stomach and the descending colon were distended at constant volume by injecting warm Ringer solution into intravisceral balloons (0.8 and 0.25 l respectively) while preventing changes in heart rate and arterial blood pressure. Distensions of the stomach or the descending colon caused a decrease in mean coronary blood flow in each pig. However, the decrease elicited by gastric distension occurred only during diastole, while the decrease caused by descending colon distension involved both systolic and diastolic coronary blood flows. The same effects on phasic coronary blood flow were observed during experiments in which the decreases in mean coronary blood flow elicited by distension of the stomach or the descending colon were further augmented by adding the distension of the second viscerum. The results indicate that the coronary vasoconstriction caused by gastric distension mainly involves the vessels which supply the subendocardial layers of the myocardium, while that caused by descending colon distension also involves the vessels which supply the subepicardial layers. The vasoconstrictor effect on the subendocardial coronary circulation is enhanced by the combined distension of the two viscera.

Animals↗

Pneumatosis in the descending colon: preliminary observations on the value of prone positioning.

Prone positioning is valuable for accurate diagnosis of intramural air in the descending colon. In the supine position, partial collapse of the descending colon can minic intramural air. Conversely, complete collapse of the descending colon eliminates the interface between intraluminal and intramural air so that the recognition of intramural air is obscured. The tendency for the descending colon to distend with gas in the prone position may reduce these false positives and negatives for intramural air.

Air↗

Development of the descending colon during the human foetal period.

The growth, changes in shape, topography and relation to the peritoneum of the descending colon were assessed on the basis of material taken from 178 foetuses of both sexes, aged from 72 to 236 days of pregnancy. The statistical analysis method demonstrated that the descending colon growth process occurs about a month earlier in female foetuses as compared to male ones. From the statistical point of view, the longitudinal growth of the descending colon significantly slows down in the 7th and 8th months of pregnancy, while the width of this part of the large intestine increases sharply towards the end of the foetal development period. The statistically important process of the descending colon rising over the surface of the left kidney and adrenal gland was noticed in male foetuses. This occurs approximately one month earlier in female foetuses as compared to males. The ascent of this part of the colon is accompanied by a change in its shape from straight, to curved and, finally, to wavy in the oldest age group of male foetuses. The changes in relation to the peritoneum are manifest in a gradual change in the position of this section of the intestine from the intraperitoneal, where more than 40% of the cases examined had a fully movable mesentery, to the extraperitoneal, with 14% of foetuses having a mesentery in the 8th month of pregnancy.

Colon, Descending↗

Efferent limb of the coronary vasoconstrictor reflex elicited by distension of the descending colon in anesthetized dogs.

Distension of the descending colon elicits reflex coronary vasoconstriction. To study the efferent branch of this reflex, experiments were performed on 5 dogs anesthetized with pentobarbitone. A pouch was formed from the distal 15 cm of the descending colon and distended at constant pressure (54 +/- 8.9 mmHg) with warm Ringer solution from a pressurized bottle. During distensions of the colon, arterial blood pressure and heart rate were kept constant by the withdrawal of blood and pacing of the heart, respectively. Experiments were performed before and after intravenous bretylium tosylate (10 mg/kg), a compound which prevents the outflow of catecholamines from the sympathetic postganglionic neurons. Before chemical sympathectomy, colon distension at constant heart rate and blood pressure caused a decrease in mean coronary blood flow by 7 +/- 3.3% (mean +/- SD, p less than 0.0005). This response was abolished after the administration of bretylium (-0.07 +/- 0.95%, p greater than 0.40). We conclude that the efferent branch of the reflex coronary vasoconstriction elicited by colon distension is through sympathetic nerves.

Animals↗

Comparison of fluid absorption by bovine and ovine descending colon in vitro.

Although bovine and ovine descending colon absorbed solute and sodium at approximately the same rate in vitro, water absorption by bovine colon was faster (15.0 +/- 2.0 microliters.h-1.cm-2, n = 8) than by ovine colon (8.6 +/- 1.3 microliters.h-1.cm-2, n = 9; P less than 0.01). Consequently, the observed osmolality of cattle absorbate was lower (364 +/- 13 mosmol/kg, n = 8) than with sheep (807 +/- 135 mosmol/kg, n = 9; P less than 0.01). Paracellular permselectivity was examined to elucidate this difference; the permeability of bovine descending colon to [3H]polyethylene glycol 400 and 4000 was higher than in sheep (P less than 0.001). A paracellular solvent drag was observed in bovine but not in ovine colon, and the electrical resistance of bovine colon was lower (16.0 +/- 1.4 omega.cm2) than ovine colon (28.0 +/- 2.4 omega.cm2; P less than 0.001). Pore radii of 2.5 nm for ovine and 5 nm for bovine colonic paracellular route were estimated from these data. It is concluded that an increased hydraulic conductance of the "active" route for solute absorption combined with raised solute reflux via the wider paracellular pathway may account for the failure of cattle to form a hypertonic absorbate and, consequently, hard feces.

Animals↗