PMID- 16973914 OWN - NLM STAT- MEDLINE DCOM- 20070322 LR - 20181201 IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 292 IP - 1 DP - 2007 Jan TI - The peristaltic reflex induced by short-chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF. PG - G429-37 AB - Short-chain fatty acids (SCFAs) accelerate colonic transit. This study examined whether this action was mediated by activation of the peristaltic reflex. SCFAs (acetate, butyrate, or propionate) were applied to the central compartment of a three-compartment flat-sheet preparation of the rat middle to distal colon. The release of serotonin (5-HT), brain-derived neurotrophic factor (BDNF), and CGRP was measured in all three compartments. Ascending contraction and descending relaxation were measured in the orad and caudad compartments. The addition of SCFAs at physiological to supraphysiological concentrations (0.5-100 mM) to the central compartment elicited concentration-dependent ascending contraction and descending relaxation (EC50 approximately 5 mM). At this concentration, SCFAs induced an 8- to 11-fold increase in 5-HT release and a 2- to 3-fold increase in CGRP release in the central compartment only. They had no effect on BDNF release. CGRP release was inhibited by a 5-HT4 but not a 5-HT3 receptor antagonist. Ascending contraction and descending relaxation were also inhibited by 5-HT4 and by CGRP receptor antagonists added to the central compartment. 5-HT and CGRP release, as well as ascending contraction and descending relaxation induced by mechanical stimulation of the mucosa (2-8 strokes), were significantly augmented by 1 mM acetate. Acetate (1 mM) also doubled propulsive velocity in isolated whole segments of the guinea pig colon. In conclusion, chemical stimulation of the mucosa by SCFAs triggers a peristaltic reflex mediated by the release of 5-HT from mucosal cells and activation of 5-HT4 receptors on sensory CGRP-containing nerve terminals. This SCFA-induced peristaltic pathway augments the peristaltic reflex elicited by mechanical stimulation of the mucosa. FAU - Grider, J R AU - Grider JR AD - Department of Physiology, Virginia Commonwealth Univ., Box 980551, Richmond, VA 23298, USA. jgrider@vcu.edu FAU - Piland, B E AU - Piland BE LA - eng GR - R01 DK034153/DK/NIDDK NIH HHS/United States GR - DK-34153/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060914 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcitonin Gene-Related Peptide Receptor Antagonists) RN - 0 (Fatty Acids, Nonesterified) RN - 333DO1RDJY (Serotonin) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) RN - Q40Q9N063P (Acetic Acid) SB - IM MH - Acetic Acid/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Calcitonin Gene-Related Peptide/*metabolism MH - Calcitonin Gene-Related Peptide Receptor Antagonists MH - Colon/drug effects/*physiology MH - Fatty Acids, Nonesterified/*pharmacology MH - Intestinal Mucosa/drug effects/physiology MH - Kinetics MH - Muscle, Smooth/drug effects/physiology MH - Peristalsis/drug effects/*physiology MH - Physical Stimulation MH - Rats MH - Serotonin/*metabolism EDAT- 2006/09/16 09:00 MHDA- 2007/03/23 09:00 CRDT- 2006/09/16 09:00 PHST- 2006/09/16 09:00 [pubmed] PHST- 2007/03/23 09:00 [medline] PHST- 2006/09/16 09:00 [entrez] AID - 00376.2006 [pii] AID - 10.1152/ajpgi.00376.2006 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G429-37. doi: 10.1152/ajpgi.00376.2006. Epub 2006 Sep 14.