Effect of 5-hydroxytryptamine on duodenal mucosal bicarbonate secretion in mice

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 125; no. 3; p. 805
• Main Authors: Tuo, Bi-Guang, Isenberg, Jon I
• Format: Journal Article
• Language: English
• Published: United States 01.09.2003
• Subjects: Acetylcholine - metabolism; Animals; Atropine - pharmacology; Bicarbonates - metabolism; Chlorides - metabolism; Dose-Response Relationship, Drug; Duodenum - drug effects; Duodenum - metabolism; Intestinal Mucosa - metabolism; Mice; NG-Nitroarginine Methyl Ester - pharmacology; Phentolamine - pharmacology; Propranolol - pharmacology; Serotonin - pharmacology; Tetrodotoxin - pharmacology
• ISSN: 0016-5085
• DOI: 10.1016/S0016-5085(03)01045-X

5-hydroxytryptamine (5-HT) is an important neurotransmitter and intercellular messenger that modulates many gastrointestinal functions. Because little is known about the role of 5-HT in the regulation of duodenal bicarbonate secretion, we examined the role of 5-HT on duodenal bicarbonate secretion and define neural pathways involved in the actions of 5-HT. Duodenal mucosa from National Institutes of Health Swiss mice was stripped of seromuscular layers and mounted in Ussing chambers. The effect of 5-HT on duodenal bicarbonate secretion was determined by the pH stat technique. Acetylcholine (ACh) release from duodenal mucosa was assessed by preincubating the tissue with [(3)H] choline and measuring 5-HT-evoked release of tritium. 5-HT added to the serosal bath markedly stimulated duodenal bicarbonate secretion and short circuit current (Isc) in a dose-dependent manner (10(-7) mol/L to 10(-3) mol/L; P < 0.0001), whereas mucosally added 5-HT was without effect. 5-HT-stimulated bicarbonate secretion was independent of luminal Cl(-). Pretreatment with tetrodotoxin (TTX) (10(-6) mol/L) or atropine (10(-5) mol/L) markedly reduced 5-HT-stimulated duodenal bicarbonate secretion (by 60% and 65%, respectively; P < 0.001) and Isc (by 45% and 27%, respectively; P < 0.001 and P < 0.05). Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME) (10(-3) mol/L), propranolol (10(-5) mol/L), or phentolamine (10(-5) mol/L) did not significantly alter 5-HT-stimulated duodenal mucosal bicarbonate secretion or Isc. 5-HT concentration-dependently evoked ACh release from duodenal mucosal preparations (P < 0.0001). TTX markedly inhibited 5-HT-evoked ACh release (P < 0.001). 5-HT is a potent activator of duodenal mucosal bicarbonate secretion in mice. Duodenal bicarbonate secretion induced by 5-HT in vitro occurs principally via a cholinergic neural pathway.