Cholinergic regulation of human proximal duodenal mucosal bicarbonate secretion

Abstract

Cephalic-vagal stimulation affects a number of upper gastrointestinal secretory and motility events. The purpose of this study was to examine the role of vagal-cholinergic regulation on human proximal duodenal mucosal HCO-3 secretion. The duodenal bulb was isolated between balloons and perfused with 154 mM NaCl, and HCO-3 secretion was measured. Although cholinergic stimulation with bethanechol (50 micrograms.kg-1.h-1 iv) produced systemic effects, resting HCO-3 secretion was unchanged. Cephalic-vagal stimulation, induced by sham feeding, significantly increased duodenal HCO-3 secretion from a basal of 177 +/- 17 to 240 +/- 19 mumols.cm-1.h-1 (P less than 0.02). The response to sham feeding was approximately 50% of the peak response to acid-stimulated HCO-3 output. Atropine (22 micrograms/kg iv) inhibited basal HCO-3 secretion significantly (79 +/- 5%). However, the net incremental increases in duodenal mucosal HCO-3 secretion in response to luminal acidification and vagal stimulation were unaltered by atropine pretreatment. Additionally, indomethacin (100 mg po) failed to modify the response to vagal-stimulated HCO-3 secretion. These findings indicate that basal human proximal duodenal mucosal HCO-3 secretion is maintained largely by resting cholinergic innervation and is stimulated by cephalic-vagal stimulation. Furthermore, since the incremental HCO-3 responses to cephalic-vagal stimulation and luminal acidification were unaltered by atropine pretreatment, each is likely mediated by noncholinergic mechanisms.

Food-induced expression of orexin receptors in rat duodenal mucosa regulates the bicarbonate secretory response to orexin-A

“…A role for cholinergic mechanisms in orexin action on the contractility of guinea pig ileum has previously been shown (33) and many of the central actions of orexins are mediated by cholinergic mechanisms (40). Muscarinic stimulation causes potent stimulation of duodenal secretion in all species tested in vivo and in vitro (2,8,20,22,36) and atropine abolished the secretory response to the muscarinic subtypeindependent agonist bethanechol in the present study (Fig. 4).…”

Role of Protein Kinases on Acid-Induced Duodenal Bicarbonate Secretion in Rats

“…Calcium signaling plays an important role in the intestinal epithelial transport, including bicarbonate secretion [20][21][22]. Calcium channel inhibitors block DBS augmented by cholinergic agents, such as carbachol and bethanechol [23][24][25][26]. Carbachol elicits a Ca 2+ spike in isolated enterocytes from human and rat duodenum [27].…”

Role of Protein Kinase C in Duodenal Mucosal Bicarbonate Secretion in the Guinea Pig

“…There are, however, data suggesting that a non-cAMP pathway may also affect DBS. Electrical vagal stimulation [4] and the mcholinoceptor agonists, carbachol [5][6][7] and bethanechol [8], stimulate DBS in laboratory animals and man. Prostaglandin F2a (PGF2a) and dibutyryl 3',5'-cyclic guanosine monophosphatate (dBcGMP) are agonists of this secretion [9].…”