Activation of submucosal 5-HT(3) receptors elicits a somatostatin-dependent inhibition of ion secretion in rat colon.
OBJECTIVE
5-Hydroxytryptamine (5-HT) is a key regulator of the gastrointestinal system and we have shown that submucosal neuronal 5-HT(3) receptors exerted a novel inhibitory effect on colonic ion transport. The aim of the present study was to investigate the precise mechanism(s) underlying this inhibitory effect.


METHODS
Mucosa/submucosa or mucosa-only preparations from rat distal colon were mounted in Ussing chambers for measurement of short-circuit current (I(sc)) as an indicator of ion secretion. Somatostatin release was determined with radioimmunoassay. Intracellular cAMP content was measured with enzyme-linked immunoadsorbent assay (elisa). Immunohistochemical techniques were used to study the expression of 5-HT(3) receptors, somatostatin and somatostatin receptors in colonic tissue.


RESULTS
In rat distal colonic mucosa/submucosa preparations, pretreatment with 5-HT(3) receptor antagonists enhanced 5-HT-induced increases in I(sc). However, in mucosa-only preparations without retained neural elements, pretreatment with 5-HT(3) receptor antagonists inhibited 5-HT-induced DeltaI(sc). Pretreatment with a somatostatin-2 (sst(2)) receptor antagonist in mucosa/submucosa preparations augmented 5-HT-induced DeltaI(sc). Combination of sst(2) and 5-HT(3) receptor antagonists did not cause further enhancement of 5-HT-induced DeltaI(sc). Moreover, both sst(2) and 5-HT(3) receptor antagonists enhanced 5-HT-induced increase in intracellular cAMP concentration in the mucosa/submucosa preparations. 5-HT released somatostatin from rat colonic mucosa/submucosa preparations, an effect prevented by pretreatment with 5-HT(3) receptor antagonists. Immunohistochemical staining demonstrated the presence of 5-HT(3) receptors on submucosal somatostatin neurons and of sst(2) receptors on colonic mucosa.


CONCLUSIONS
Activation of neuronal 5-HT(3) receptors in the submucosal plexus of rat colon suppressed 5-HT-induced ion secretion by releasing somatostatin from submucosal neurons.
Department of Physiology, Capital Medical University, Beijing, China.
N
N
Yang
S M
SM
Liu
L F
LF
Zheng
T
T
Ji
Y
Y
Li
X L
XL
Mi
H
H
Xue
W
W
Ren
J D
JD
Xu
X H
XH
Zhang
L S
LS
Li
Y
Y
Zhang
J X
JX
Zhu
D000595:Amino Acid Sequence; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007477:Ions; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013004:Somatostatin / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
C403089:CYN 154806; D007477:Ions; D009842:Oligopeptides; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D013779:Tetrodotoxin; D013004:Somatostatin; D000242:Cyclic AMP