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

Abstract

.-Submucosal cholinergic and noncholinergic neurons in intestines have been shown to be involved in regulating epithelial transport functions, particularly stimulating Cl Ϫ secretion. This study investigates the role of submucosal cholinergic neurons in regulating electrogenic Na ϩ absorption in distal colon. Amiloride-sensitive short-circuit current (Isc) and 22 Na ϩ flux were measured in mucosal and mucosalsubmucosal preparations mounted in Ussing chambers. In the mucosal preparation, carbachol (CCh) added to the serosal side inhibited amiloride-sensitive Isc and amiloride-sensitive 22 Na ϩ absorption. The inhibitory effect of CCh was observed at ϳ0.1 M, and maximum inhibition of ϳ70% was attained at ϳ30 M (IC50 ϭ ϳ1 M). CCh-induced inhibition of amiloride-sensitive Isc was almost totally abolished by 10 M atropine. Treatment of the tissue with ionomycin markedly reduced amiloride-sensitive Isc, but a subsequent addition of CCh further decreased it. Also, CCh still had an inhibitory effect, although significantly attenuated, after the tissue had been incubated with a low-Ca 2ϩ solution containing ionomycin and BAPTA-AM. Applying electrical field stimulation to submucosal neurons in the mucosal-submucosal preparation resulted in inhibition of amiloride-sensitive Isc, ϳ33% of this inhibition being atropine sensitive. Physostigmine inhibited amiloride-sensitive Isc, this effect being abolished by atropine. In conclusion, submucosal cholinergic and noncholinergic neurons were involved in inhibiting electrogenic Na ϩ absorption in colon. This inhibition by cholinergic neurons was mediated by muscarinic receptor activation. enteric nerve; intracellular Ca 2ϩ ; acetylcholine; intestinal secretion; epithelial Na ϩ channel THE COLON, THE TERMINAL PART of the gastrointestinal tract, performs functions of both absorption and secretion of a variety of electrolytes by epithelial transport systems. Regulation of this absorption and secretion of electrolytes by neurocrine, paracrine, and endocrine systems probably plays an important role in maintaining the fluid and electrolyte homeostasis in the whole body as well as being involved in mucosal defensive functions (1, 25).The colon, like other segments of the gastrointestinal tract, has an intrinsic nervous system, the enteric nervous system, consisting of two ganglionated plexi, namely the myenteric plexus and the submucosal plexus (also called the submucous plexus). Myenteric neurons mainly regulate contractile activity, whereas submucosal neurons are mainly involved with epithelial transport functions (5, 12). It has been shown that the stimulation of submucosal neurons by electrical, mechanical, or pharmacological means led to enhanced Cl Ϫ secretion (5, 12). In addition, the inhibition of electroneutral NaCl absorption (3, 23) and stimulation of K ϩ secretion (6,15,16,28) are also likely to be induced by submucosal neurons. Cholinergic neurons are predominantly responsible for these epithelial prosecretory responses, although neurons containing vasoactive intestinal pept...

Intracellular Ca2+and Zn2+signals during monochloramine-induced oxidative stress in isolated rat colon crypts

“…These observations raise intriguing questions regarding the structural specificity of different reactive nitrogen species, their targets, and potential intracellular pools buffering against their activity (thiol-rich molecules such as glutathione, metallothionein, etc). It is well recognized that increases in [Ca 2ϩ ] i trigger secretion in colon crypts (8,51,72,73) and inhibit absorption in surface epithelium (28,79), considered a "flushing" response that clears luminal bacteria and other noxious agents away from the mucosal surface (53,57). In diverse in vitro cell culture models, agonist-stimulated increases in [Ca 2ϩ ] i enhance mitochondrial respiration and substrate utilization (34,66).…”

Acetylcholinesterase supports anchorage independence in colon cancer

“…Cholinesterases are physiologically present in colon, mostly in the ganglia, and the cholinergic innervation of the intestines is important for motor activity [10], muscle tone [11,12], and epithelial absorption [13]. Colon epithelial cells originate in the crypts and move up the villi.…”

Regulation of Drug Absorption from Small Intestine by Enteric Nervous System I: a Poorly Absorbable Drug Via Passive Diffusion

“…It is well know that ENS regulates the motility [1][2][3][11][12][13] and function [4][5]12,[14][15][16][17] of gastrointestinal tract. However, the eŠect of ENS on drug absorption from the small intestine has never been systematically investigated.…”

“…[1][2][3] On the other hand, submucosal ganglia embedded in the submucosa and submucosal neurons are mainly involved with epithelial function and blood ‰ow. [4][5] Interconnectingˆbers between the myenteric and submucosal plexuses function to coordinate motility and transport functions. 5) F r o mt h ea s p e c to ft y p eo f neurons, ENS is composed of cholinergic, adrenergic and nonadrenergic noncholinergic (NANC) neurons.…”

“…10) The eŠect of ENS on the small-intestinal functions has been intensively studied in respect to the regulation of the smooth muscle [1][2][3][11][12][13] and the transport of water and W or electrolytes. [4][5]12,[14][15][16][17] However, the information about the eŠect of ENS on the membrane permeability of the gastrointestinal tract is very limited 12,16,18) and the regulation of drug absorption by ENS has never been systematically evaluated.…”