Somatostatin monoclonal antibody immunoneutralization increases gastrin and gastric acid secretion in urethane-anesthetized rats

Yang, Hong; Wong, Helen; Wu, Vincent; Walsh, John H.; Taché, Yvette

doi:10.1016/0016-5085(90)90952-w

Cited by 69 publications

(25 citation statements)

References 22 publications

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“…In this urethane model, fasting plasma levels of acyl ghrelin were inhibited and the sst 2 antagonist injected iv restored ghrelin levels within 0.5 h to those observed in fasted conscious nontreated rats. We previously demonstrated that urethane under similar conditions induces a somatostatin-dependent inhibition of plasma levels of gastrin (71). The present findings expand the inhibitory effect of urethane mediated by the activation of somatostatin signaling to another gastric hormone, acyl ghrelin.…”

Section: Discussionsupporting

confidence: 80%

“…The partial reduction at 1 h could be due to the relatively short half-life of the compound as previously reported for another peptide sst 2 antagonist (35). We also used urethane anesthesia, known to increase rat gastric somatostatin mRNA levels and activate endogenous gastric somatostatin signaling within 30 min postinjection (71). In this urethane model, fasting plasma levels of acyl ghrelin were inhibited and the sst 2 antagonist injected iv restored ghrelin levels within 0.5 h to those observed in fasted conscious nontreated rats.…”

Section: Discussionmentioning

confidence: 96%

“…Conscious rats were injected iv (200 l) with the sst2 antagonist S-406-028 (100 g/rat) or vehicle followed by intraperitoneal injection of 25% urethane (1 ml/300 g body wt) known to increase gastric somatostatin mRNA expression and peptide release (71). The control group did not receive any treatment.…”

Section: Experimental Protocolsmentioning

confidence: 99%

“…We first assessed the acyl ghrelin response and sst 2 antagonist effect to an intraperitoneal injection of 25% urethane known to induce a somatostatin-dependent inhibition of circulating gastrin and gastric acid secretion (71). Urethane decreased fasting acyl and desacyl ghrelin plasma levels within 30 min by 36 and 32%, respectively, in iv vehicle-injected rats compared with overnight-fasted conscious nontreated rats (P Ͻ 0.05; Fig.…”

Section: The Sst 2 Antagonist Prevents the Abdominal Surgery-induced mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 96%

Section: Experimental Protocolsmentioning

confidence: 99%

Section: The Sst 2 Antagonist Prevents the Abdominal Surgery-induced mentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

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“…Hence, in the present study, we used urethane as our anesthetic of choice because it has been reported not to augment GABA A receptor signaling in the NTS (1). Urethane does augment other types of signaling, e.g., signaling mediated by somatostatin (40), but how this altered signaling would influence our results is difficult to interpret without knowing what role, if any, somatostatin plays in the vagovagal reflex circuitry controlling gastric motility.…”

Section: Discussionmentioning

confidence: 91%

GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit

Herman

Cruz²,

Sahibzada³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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It has been proposed that there is an "apparent monosynaptic" connection between gastric vagal afferent nerve terminals and inhibitory projection neurons in the nucleus tractus solitarius (NTS) and that two efferent parallel pathways from the dorsal motor nucleus of the vagus (DMV) influence peripheral organs associated with these reflexes (6). The purpose of our study was to verify the validity of these views as they relate to basal control of gastric motility. To test the validity of a direct connection of vagal afferent terminals (known to release L-glutamate) directly impacting second-order projection neurons, we evaluated the effect of GABA A receptor blockade in the area of the medial subnucleus of the tractus solitarius (mNTS) on gastric motility. Microinjection of bicuculline methiodide into the mNTS produced robust decreases in gastric motility (Ϫ1.6 Ϯ 0.2 mmHg, P Ͻ 0.05, n ϭ 23), which were prevented by cervical vagotomy and by pretreatment with kynurenic acid microinjected into the mNTS. Kynurenic acid per se had no effect on gastric motility. However, after GABA A receptor blockade in the mNTS, kynurenic acid produced a robust increase in gastric motility. To test for the contribution of two parallel efferent DMV pathways, we assessed the effect of either intravenous atropine methylbromide or N G -nitro-L-arginine methyl ester on baseline motility and on decreases in gastric motility induced by GABA A receptor blockade in the mNTS. Only atropine methylbromide altered baseline motility and prevented the effects of GABA A receptor blockade on gastric motility. Our data demonstrate the presence of intra-NTS GABAergic signaling between the vagal afferent nerve terminals and inhibitory projection neurons in the NTS and that the cholinergic-cholinergic excitatory pathway comprises the functionally relevant efferent arm of the vagovagal circuit. gastric; vagus; afferent; inhibition; rat THE IMPORTANCE OF THE VAGOVAGAL reflexes in the regulation of gastrointestinal (GI) function has been highlighted in a recent series of articles published under the theme "Musings on the Wanderer: What's New in Our Understanding of Vagovagal Reflexes?" (6, 37). The central nervous system component of this reflex circuit is located in the hindbrain and consists of a sensory nucleus, the nucleus tractus solitarius (NTS), and a motor nucleus, the dorsal motor nucleus of the vagus (DMV). Currently it is thought that signals from sensory receptors in the GI tract are received in the NTS and conveyed to DMV preganglionic vagal nerves (28, 36). These impulses produce functional changes in thoracic and abdominal viscera (28, 36). Critical to conveying sensory signals to vagal efferent impulses are synaptic connections between NTS and DMV neurons. There is considerable evidence that GABAergic neurons are responsible for a significant part of this communication (9, 35). There is also evidence that noradrenergic neurons take part in this communication process (10,11,18,26,29). Both the GABAergic and noradrenergic neurons are considered...

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Gastric Peptides—Gastrin and Somatostatin

Schubert

Rehfeld

2019

Comprehensive Physiology

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Somatostatin monoclonal antibody immunoneutralization increases gastrin and gastric acid secretion in urethane-anesthetized rats

Cited by 69 publications

References 22 publications

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

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

GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit

Gastric Peptides—Gastrin and Somatostatin

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