Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P20366 (
substance P
)
21,176
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The effects of
xenin
25, a peptide of the neurotensin/xenopsin family, were examined on the motility of the guinea pig jejunum and colon in vitro. In the jejunum,
xenin
induced a biphasic response: first a small relaxation and then a large contraction. In the colon,
xenin
induced relaxation. The tenia coli was contracted. Deletion or amidation of the C-terminal leucine inactivated
xenin
. A peptide sequence of 16 C-terminal amino acids was necessary to elicit a full response in the jejunum, whereas in the colon, the potencies of all fragments of
xenin
25, including the 6 C-terminal amino acid sequence (
xenin
6), were not significantly different from that of
xenin
25. In the jejunum, contraction was abolished or reduced by tetrodotoxin, by atropine, by met-enkephalin, by antagonists to the
tachykinin
receptors NK1 and NK2 and by the P2-purinoceptor antagonist suramin. L-NNA, phentolamine, methysergide, hexamethonium and apamin had no effect. In the colon, all actions of
xenin
were tetrodotoxin-resistant; the potency of
xenin
to relax was reduced by apamin and suramin. The actions of
xenin
on small and large bowel were attenuated by the neurotensin receptor antagonist SR 48692. The
xenin
analog neurotensin was significantly less potent than
xenin
25 in contracting the jejunum and more potent than
xenin
25 in relaxing the colon. We conclude that
xenin
exerts excitatory effects on a neuronal subtype receptor in the jejunum, with participation of muscarinic, purinergic and
tachykinin
-related mechanisms.
Xenin
exerts relaxing effects on the colon by interaction with a myokinetic subtype receptor involving Ca(++)-dependent K+ channels and the P2-purinoceptor.
...
PMID:Neurokinetic and myokinetic effects of the peptide xenin on the motility of the small and large intestine of guinea pig. 876 16
Xenin
-25, a neurotensin (NT)-related anorexigenic gut hormone generated mostly in the duodenal mucosa, is believed to increase the rate of duodenal ion secretion, because
xenin
-induced diarrhea is not present after Roux-en-Y gastric bypass surgery. Because the local effects of
xenin
on duodenal ion secretion have remained uninvestigated, we thus examined the neural pathways underlying
xenin
-induced duodenal anion secretion. Intravenous infusion of
xenin
-8, a bioactive C-terminal fragment of
xenin
-25, dose dependently increased the rate of duodenal HCO
3
-
secretion in perfused duodenal loops of anesthetized rats.
Xenin
was immunolocalized to a subset of enteroendocrine cells in the rat duodenum. The mRNA of the
xenin
/NT receptor 1 (NTS1) was predominantly expressed in the enteric plexus, nodose and dorsal root ganglia, and in the lamina propria rather than in the epithelium. The serosal application of
xenin
-8 or
xenin
-25 rapidly and transiently increased short-circuit current in Ussing-chambered mucosa-submucosa preparations in a concentration-dependent manner in the duodenum and jejunum, but less so in the ileum and colon. The selective antagonist for NTS1,
substance P
(SP) receptor (NK1), or 5-hydroxytryptamine (5-HT)
3
, but not NTS2, inhibited the responses to
xenin
.
Xenin
-evoked Cl
-
secretion was reduced by tetrodotoxin (TTX) or capsaicin-pretreatment, and abolished by the inhibitor of TTX-resistant sodium channel Nav1.8 in combination with TTX, suggesting that peripheral
xenin
augments duodenal HCO
3
-
and Cl
-
secretion through NTS1 activation on intrinsic and extrinsic afferent nerves, followed by release of SP and 5-HT. Afferent nerve activation by postprandial, peripherally released
xenin
may account for its secretory effects in the duodenum.
...
PMID:Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways. 2811 52
Xenin
-25 is a neurotensin-like peptide that is secreted by enteroendocrine cells in the small intestine.
Xenin
-8 is reported to augment duodenal anion secretion by activating afferent neural pathways. The intrinsic neuronal circuits mediating the
xenin
-25-induced anion secretion were characterized using the Ussing-chambered, mucosa-submucosa preparation from the rat ileum. Serosal application of
xenin
-25 increased the short-circuit current in a concentration-dependent manner. The responses were abolished by the combination of Cl
-
-free and
HCO
3
-
-free solutions. The responses were almost completely blocked by TTX (10
-6
M) but not by atropine (10
-5
M) or hexamethonium (10
-4
M). The selective antagonists for neurotensin receptor 1 (NTSR1),
neurokinin 1
(
NK1
), vasoactive intestinal polypeptide (VIP) receptors 1 and 2 (VPAC1 and VPAC2, respectively), and capsaicin, but not 5-hydroxyltryptamine receptors 3 and 4 (5-HT
3
and 5-HT
4
), NTSR2, and A803467, inhibited the responses to
xenin
-25. The expression of VIP receptors (
Vipr
) in rat ileum was examined using RT-PCR. The
Vipr1
PCR products were detected in the submucosal plexus and mucosa. Immunohistochemical staining showed the colocalization of NTSR1 and
NK1
with
substance P
(SP)- and calbindin-immunoreactive neurons in the submucosal plexus, respectively. In addition,
NK1
was colocalized with noncholinergic VIP secretomotor neurons. Based on the results from the present study,
xenin
-25-induced Cl
-
/
HCO
3
-
secretion is involved in NTSR1 activation on intrinsic and extrinsic afferent neurons, followed by the release of SP and subsequent activation of
NK1
expressed on noncholinergic VIP secretomotor neurons. Finally, the secreted VIP may activate VPAC1 on epithelial cells to induce Cl
-
/
HCO
3
-
secretion in the rat ileum. Activation of noncholinergic VIP secretomotor neurons by intrinsic primary afferent neurons and extrinsic afferent neurons by postprandially released
xenin
-25 may account for most of the neurogenic secretory response induced by
xenin
-25.
NEW & NOTEWORTHY
This study is the first to investigate the intrinsic neuronal circuit responsible for
xenin
-25-induced anion secretion in the rat small intestine. We have found that nutrient-stimulated
xenin
-25 release may activate noncholinergic vasoactive intestinal polypeptide (VIP) secretomotor neurons to promote Cl
-
/
HCO
3
-
secretion through the activation of VIP receptor 1 on epithelial cells. Moreover, the
xenin
-25-induced secretory responses are mainly linked with intrinsic primary afferent neurons, which are involved in the activation of neurotensin receptor 1 and neurokinin 1 receptor.
...
PMID:Xenin-25 induces anion secretion by activating noncholinergic secretomotor neurons in the rat ileum. 3097 13
