Alimentary Tract5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine☆,☆☆
Section snippets
Compartmented flat-sheet preparation of guinea pig and rat colon
A three-compartment flat-sheet preparation previously described in detail1, 2 was used to measure neurotransmitter release and contraction or relaxation of circular muscle. In brief, 5-cm segments of mid-to-distal colon were opened and pinned mucosal side up to the base of a chamber and bathed in a Krebs-bicarbonate medium containing 118 mmol/L NaCl, 4.8 mmol/L KCl, 1.2 mmol/L KH2PO4, 2.5 mmol/L CaCl2, 1.2 mmol/L MgSO4, 25 mmol/L NaH2CO3, 11 mmol/L glucose, 0.1% bovine serum albumin, 10 μmol/L
Release of CGRP by the 5-HT4 agonist HTF 919
Addition of HTF 919 to the central compartment caused a concentration-dependent release of CGRP into the central compartment but not into the peripheral orad or caudad compartments in rat and guinea pig colon (Figure 1).
Discussion
The study shows that selective 5-HT4 agonists added to the intestinal mucosa trigger the peristaltic reflex: the sequence involves activation of CGRP-containing sensory nerves resulting in release of excitatory and inhibitory neurotransmitters that regulate the orad and caudad phases of the reflex (Figure 11).
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Address requests for reprints to: John R. Grider, Ph.D., Box 980551, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0551. e-mail: [email protected]; fax: (804) 828-2500.
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Supported by grant DK34153 from the National Institute of Diabetes and Digestive and Kidney Diseases.