Somatostatin 2A receptor is expressed by enteric neurons, and by interstitial cells of Cajal and enterochromaffin-like cells of the gastrointestinal tract

Sternini, Catia; Wong, Helen; Wu, S. Vincent; Georgio, Roberto de; Yang, Moon Young; Reeve, Joseph R.; Brecha, Nicholas C.; Walsh, John H.

doi:10.1002/(sici)1096-9861(19970929)386:3<396::aid-cne5>3.0.co;2-x

Cited by 93 publications

(62 citation statements)

References 61 publications

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“…The small decrease in somatostatin during the ascending phase did not seem to be functionally relevant, because immunoneutralization of somatostatin and application of agonists and antagonists of various somatostatin receptor subtypes had no effect on ascending contraction. The participation of SSTR2 receptors in the peristaltic reflex is consistent with immunohistochemical studies demonstrating the presence of SSTR2 receptors on enteric neurons containing VIP and NO in rat and mouse (Sternini et al, 1997;Allen et al, 2002). These findings raise the possibility of an alternative parallel pathway in which the projection of SST is directly to the inhibitory motor neuron.…”

supporting

confidence: 85%

Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse

Grider

2003

J Pharmacol Exp Ther

154

168

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The motor, modulatory, and sensory neurotransmitters that mediate the peristaltic reflex in the mouse colon were identified by direct measurement, and their involvement in various pathways was determined by selective receptor antagonists. Mucosal stimulation in the central compartment of a three-compartment flat sheet preparation of mouse colon elicited ascending contraction and descending relaxation in the orad and caudad compartments, respectively. Ascending contraction was accompanied by substance P release, a marker for excitatory neurotransmitter release, into the orad compartment and was partly inhibited by atropine and spantide, and abolished by a combination of the two antagonists. Descending relaxation was accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release, into the caudad compartment, and was partly inhibited by VIP [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] and N G -nitro-L-arginine, and abolished by a combination of the two agents. Somatostatin release increased during descending relaxation: immunoneutralization of somatostatin or blockade of its effect with a selective somatostatin type 2 receptor antagonist inhibited descending relaxation. The ␦-opioid receptor antagonist naltrindole augmented descending relaxation and ascending contraction. Calcitonin gene-related peptide (CGRP) release increased in the central compartment and was mediated by concurrent release of 5-hydroxytryptamine (5-HT) because its release was blocked by a 5-HT 4 receptor antagonist. Both the latter and the CGRP antagonist CGRP 8-37 , inhibited ascending contraction and descending relaxation. Thus, the reflex in mouse like that in rat and human intestine is initiated by mucosal release of 5-HT and activation of 5-HT 4 receptors on CGRP sensory neurons and is relayed via somatostatin and opioid interneurons to VIP/nitric-oxide synthase inhibitory motor neurons and via cholinergic interneurons to acetylcholine/tachykinin excitatory motor neurons.The intestinal peristaltic reflex is one of very few functions where the role of enteric peptide neurotransmitters has been elucidated. Several advances, including precise immunocytochemical mapping of enteric neurons, sensitive radioimmunoassay, and the availability of peptide antibodies and receptor antagonists have facilitated the identification of these neurotransmitters and their roles in the regulation of the peristaltic reflex. However, molecular tools, e.g., nonlethal knockout animals, have yet to be used extensively in identifying the neurotransmitters and receptors that mediate the peristaltic reflex, making it essential to develop techniques to characterize the reflex in mice similar to those used successfully in rats and guinea pigs.The topography of enteric neurons is generally well conserved. In the mouse, as in other mammalian species, a third of the myenteric neurons in the small intestine and colon contain vasoactive intestinal peptide (VIP) and its homolog, peptide histid...

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supporting

confidence: 85%

Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse

Grider

2003

J Pharmacol Exp Ther

154

168

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“…The molecular basis for the mediation of motor neurotransmission by ICC-IM and ICC-DMP is likely to involve expression of proteins that participate in the binding and transduction of neurotransmitters. For example, previous studies have shown that ICC express a variety of receptors, including peptide receptors, such as neurokinin (19,25,32,46), somatostatin (41) and VIP receptors (7), M 2 and M 3 muscarinic receptors (7), and nucleotide receptors (5). Expression of intracellular signaling intermediates such as protein kinases (30,40) and cGMP (38,55) is also consistent with a role for ICC-IM in mediating neuroeffector functions.…”

supporting

confidence: 58%

Selective labeling and isolation of functional classes of interstitial cells of Cajal of human and murine small intestine

Chen¹,

Redelman²,

Ro³

et al. 2007

American Journal of Physiology-Cell Physiology

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functions of interstitial cells of Cajal (ICC) have been linked to distinct classes that differ by morphology and distribution. In the small intestine, slow wavegenerating ICC are located in the myenteric region (ICC-MY), whereas ICC that mediate neuromuscular neurotransmission occur either throughout the circular muscle layer (intramuscular ICC, ICC-IM) or in association with the deep muscular plexus (ICC-DMP). Selective isolation of ICC to characterize specific properties has been difficult. Recently, neurokinin-1 receptors have been detected in murine ICC-DMP and neurons but not in ICC-MY. Here we identified and isolated ICC-DMP/IM by receptor-mediated internalization of fluorescent substance P and Kit immunofluorescence. Specificity of labeling was verified by confocal microscopy. Mouse and human ICC-DMP/IM were detected in suspension by fluorescent microscopy and harvested for RT-PCR with micropipettes. The isolated cells expressed Kit but not markers for neurons, smooth muscle, or antigenpresenting cells. ICC-DMP expressed neurokinin-1 receptor, M 2 and M 3 muscarinic receptors, P2Y1 and P2Y 4 purinergic receptors, VIP receptor 2, soluble guanylate cyclase-1 subunits, and protein kinase G. L-or T-type Ca 2ϩ channels were not detected in these cells. ICC-MY and ICC-DMP were simultaneously detected and enumerated by flow cytometry and sorted to purity by fluorescence-activated cell sorting. In summary, functional classes of ICC have distinct molecular identities that can be used to selectively identify and harvest these cells with, for example, receptor-mediated uptake of substance P and Kit immunofluorescence. ICC-DMP express neurotransmitter receptors and signaling intermediate molecules that are consistent with their role in neuromuscular neurotransmission.

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“…The CURE no. 9452 is directed against the COOH-terminus of mouse sst2a (amino acids 331-340), and its specificity was previously established (65). Fluorescein isothiocyanate (FITC)-labeled goat anti-mouse (1:1,000, Jackson ImmunoResearch Laboratories, West Grove, PA) and tetramethylrhodamine-5-(and 6)-isothiocyanate (TRITC)-conjugated goat anti-rabbit IgG (1:1,000, Jackson ImmunoResearch Laboratories) in 0.3% Triton X-100 in PBS were added for 2 h at room temperature.…”

Section: Immunofluorescent Histochemistrymentioning

confidence: 99%

Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2

Stengel

Goebel-Stengel

Wang

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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NWG, Rivier J, Taché Y. Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2. Am J Physiol Gastrointest Liver Physiol 301: G239 -G248, 2011. First published June 2, 2011; doi:10.1152/ajpgi.00018.2011.-Clinical studies are evaluating the efficacy of synthetic ghrelin agonists in postoperative ileus management. However, the control of ghrelin secretion under conditions of postoperative gastric ileus is largely unknown. Peripheral somatostatin inhibits ghrelin secretion in animals and humans. We investigated the time course of ghrelin changes postsurgery in fasted rats and whether somatostatin receptor subtype 2 (sst2) signaling is involved. Abdominal surgery (laparotomy and 1-min cecal palpation) induced a rapid and long-lasting decrease in plasma acyl ghrelin levels as shown by the 64, 67, and 59% reduction at 0.5, 2, and 5 h postsurgery, respectively, compared with sham (anesthesia alone for 10 min, P Ͻ 0.05). Levels were partly recovered at 7 h and fully restored at 24 h. The percentage of acyl ghrelin reduction was significantly higher than that of desacyl ghrelin at 2 h postsurgery and not at any other time point. This was associated with a 48 and 23% decrease in gastric and plasma ghrelin-O-acyltransferase protein concentrations, respectively (P Ͻ 0.001). Ghrelin-positive cells in the oxyntic mucosa expressed sst2a receptor and the sst2 agonist S-346-011 inhibited fasting acyl ghrelin levels by 64 and 77% at 0.5 and 2 h, respectively. The sst2 antagonist S-406-028 prevented the abdominal surgery-induced decreased circulating acyl ghrelin but not the delayed gastric emptying assessed 0.5 h postinjection. These data show that activation of sst2 receptor located on gastric X/A-like cells plays a key role in the rapid inhibition of circulating acyl ghrelin induced by abdominal surgery while not being primarily involved in the early phase of postoperative gastric ileus. gastric emptying; somatostatin receptor 2 agonist; somatostatin receptor 2 antagonist; X/A-like cell POSTOPERATIVE GASTRIC ILEUS is a condition that develops as a consequence of surgery and is associated with delayed gastric emptying and intestinal transit (41). Since prolonged postoperative ileus (POI) is an iatrogenic condition leading to prolonged hospitalization resulting in increased health care costs, the development of effective management strategies to prevent POI is clinically important (74). Recently, the food intake stimulating and gastroprokinetic effects of the peptide hormone ghrelin is gaining recognition for the treatment of POI (9). The long-acting synthetic agonist Tranzyme Pharma-101 was reported to accelerate the recovery of the upper and lower gastrointestinal tract in patients undergoing major abdominal surgery (47), consistent with preclinical evidence that peripheral administration of ghrelin agonists reversed the abdominal surgery-induced delayed gastric emptying in rats and dogs (69). However, the regulation of ghrelin under condition...

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Somatostatin 2A receptor is expressed by enteric neurons, and by interstitial cells of Cajal and enterochromaffin-like cells of the gastrointestinal tract

Cited by 93 publications

References 61 publications

Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse

Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse

Selective labeling and isolation of functional classes of interstitial cells of Cajal of human and murine small intestine

Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2

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