Luminal propionate‐induced secretory response in the rat distal colon in vitro.

Abstract

SUMMARY1. The stimulatory action of propionate on colonic electrolyte transport and involvement of the enteric reflex in this was studied in vitro using an Ussing chamber in the rat. The short-circuit current (I.,) and bidirectional fluxes of Na+ and Cl-were measured. Mucosa-submucosa preparations, containing the submucosal nerve, from the distal colon were used in most cases.2. Mucosal application of propionate caused transient increases in the transmural potential difference, with the mucosal side negative, ISc and conductance. Serosal application of the acid had no effect.3. Adaptation of the ISC response occurred when the acid was applied to the bathing solution cumulatively without washing out the first dose. If tissues were washed and held more than 20 min before the next application, the response was almost completely restored.4. The increase in IS. in response to propionate was concentration dependent, with a 50% effective concentration of approximately 7 x 10-5 M.5. Two other short-chain fatty acids (SCFAs), n-butyrate and n-valerate, but not acetate, increased ISC when added to the mucosal bathing solution.6. Bumetanide (3 x 10-5 M) and the serosal chloride-free condition, but not amiloride (10-M), inhibited the responses of ISC to propionate. Propionatestimulated Cl-secretion resulted mainly from an increase in unidirectional serosalto-mucosal C1-movement. Propionate did not affect the Na+ flux.7. Tetrodotoxin (10-7 M), somatostatin (10-7 M) and hexamethonium (10-4 M) inhibited the propionate-evoked increase in ISC by 40, 70 and 30°%, respectively.8. Atropine (10-5 M) also inhibited the I,,-increase response to propionate more than 90 %.9. Pre-treatment (2 min) of the mucosal surface with procaine (5 x 10-M)inhibited the propionate-evoked increase in IS. by 90°%.10. The results suggest that luminal propionate transiently stimulated the colonic chloride secretory response that is not due to direct action on colonocytes, but due in large part to release of acetylcholine at neuro-colonocyte junctions, probably via an enteric reflex involving a mucosal sensory mechanism, cholinergic motor nerves and submucosal ganglia.

Expression of short-chain fatty acid receptor GPR41 in the human colon

“…N-linked glycosylation of cell surface receptors is generally recognized to increase molecular stability, promote cell surface expression, and often modulate ligand binding activity (6,21), but the specific function of N-linked glycosylation of GPR41 is unclear as of yet; it may be related to higher ligand specificity as compared to GPR43. The fact that PNGase F-treated GPR41 protein still showed a higher molecular weight compared to its theoretical weight suggests that GPR41 protein might have oth- ments did not induce the previously reported responses with SCFAs (20,24). This discrepancy is not resolved in the present study, but it is possible that GPR41-expressing enteroendocrine cells contain other transmitter(s) that activate enterochromaffin cells containing 5-HT, mucosal mast cells and/or enteric neurons.…”

“…Do enteroendocrine cells containing GPR41, an acknowledged minority, play any physiological role in the ascending colon? In previous studies (23,24), the potency order of individual SCFA-induced physiological responses, including peristaltic and secretory responses, has been reported to be propionate ≧ butyrate >> acetate, as seen in GPR41, but different than GPR43 (propionate = butyrate = acetate). It is possible that these physiological functions are mediated via GPR41 rather than GPR43 even at the low GPR41 expression levels found in this study.…”

Cholinergic inhibition of electrogenic sodium absorption in the guinea pig distal colon

“…Alternatively, epithelial and nonepithelial cells exhibiting immunoreactivity to choline acetyltransferase might have been the source of tissue ACh (30,38,39). A role of tissue ACh that was independent of the cholinergic nerve activity has been previously suggested from the finding that TTX inhibited the luminal propionate-induced Cl Ϫ secretion in the colon by 40%, whereas atropine inhibited it by 90% (55).…”

“…The distal colon was excised and then opened along the root of the mesentery. A mucosal preparation consisting of the mucosal layer and a part of the muscularis mucosal layer was obtained with glass microscopic slides (55). The mucosal-submucosal preparation, consisting of the mucosal, muscularis mucosal, and submucosal layers was obtained with fine forceps.…”

<b>Desacetyl bisacodyl-induced epithelial Cl</b>^<b>−</b><b> secretion in rat colon and r</b><b>ectum </b>

“…To check tissue viability, tissues were electrically stimulated by passing a current parallel to the plane of the tissue via a pair of aluminum foil ribbon electrodes placed on the submucosal surface. Rectangular electrical field stimulation (EFS) pulses of 25 V, 5 Hz, and 0.5-ms duration were applied for 120 s. A modified Krebs-Ringer Cl − -free solution was prepared according to a previous study (13 ) secretory responses through the expression of G protein-coupled receptors on the epithelium of the colon (6,24,25). 6-n-Propyl-2-thiouracil, a bitter compound, is classified as a toxic substance.…”