Linkage between capsaicin-stimulated calcitonin gene-related peptide and somatostatin release in rat stomach

Inui, Tetsuya; Kinoshita, Yoshikazu; Yamaguchi, Akinori; Yamatani, Toshiyuki; Chiba, Tsutomu

doi:10.1152/ajpgi.1991.261.5.g770

Cited by 27 publications

(22 citation statements)

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“…Potential mechanisms may involve capsaicin-sensitive afferents containing calcitonin gene-related peptide (CGRP) signaling known to be activated by abdominal surgery (29,46,75). There is also an established linkage between capsaicin-sensitive afferent stimulation containing CGRP and the increase in gastric somatostatin release (8,34,48). Collectively, these data support the contention that the reduction of circulating ghrelin levels in rats induced by peripheral administration of somatostatin (18,55,57) or sst 2 agonist (present study) and by endogenous somatostatin released by urethane or likely by abdominal surgery involves the activation of sst 2 receptors expressed on gastric X/A-like cells.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The mechanism ofgastroprotection afforded by paren teral capsaicin has been little studied, but in case of aciddependent mucosal lesions (ASA or WRS) it could be attributed to the inhibition of gastric acid secretion possi bly mediated by locally released somatostatin [32], Fur thermore. parenteral capsaicin might stimulate the affer ent nerves and enhance the release of vasoactive neuro transmitters such as CGRP [33] which could be one of the candidates responsible for the hyperemia accompanying protection afforded by capsaicin.…”

Section: Discussionmentioning

confidence: 99%

Role of Capsaicin-Sensitive Sensory Nerves in Gastroprotection against Acid-Independent and Acid-Dependent Ulcerogens

Brzozowski

Sj²,

Śliwowski³

et al. 1996

Digestion

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Treatment with small doses of topical capsaicin protects the gastric mucosa from the damage by strong irritants but functional ablation of sensory nerves by pretreatment with larger dose of parenteral capsaicin augments the formation of gastric lesions via unknown mechanism. This study was designed to determine the role of gastric acid secretion, mucosal blood flow (GBF) and prostaglandins (PG) generation in the gastroprotection induced by small doses of topical or parenteral capsaicin in rats with intact or capsaicin-deactivated sensory nerves. Gastric lesions were produced in rats with intact sensory nerves (series A) or capsaicin-deactivated nerves (series B) using intragastric (i.g.) application of 100% ethanol, acidified aspirin (ASA) or water immersion and restraint stress (WRS). Pretreatment with i.g. capsaicin (0.12-1.0 mg/kg) in rats with intact sensory nerves (series A) reduced dose-dependently the mucosal damage caused by ethanol, ASA or WRS, the dose inhibiting the lesion area by 50% (ID₅o) being 0.3, 0.5 and 0.7 mg/kg, respectively. This protection was accompanied by a significant rise in gastric mucosal blood flow (GBF). Parenteral application of capsaicin (1.2-10 mg/kg s.c.) that in intact rats dose-dependently increased GBF, also dose-dependently reduced gastric damage induced by ASA or WRS (but not by ethanol), the ID₅₀ being 5 and 3 mg/kg, respectively. The reduction by i.g. capsaicin of ethanol- or WRS-induced mucosal lesions was accompanied by a rise in GBF and this effect was reversed by indomethacin at a dose that suppressed endogenous PG biosynthesis by about 90%, indicating that PG are involved in the protective activities of topical capsaicin. Furthermore, topical and to a lesser extent parenteral capsaicin given to rats with intact or deactivated sensory nerves inhibited gastric acid and pepsin outputs, suggesting that this inhibition could contribute to the capsaicin-induced gastroprotection against acid-dependent mucosal lesions (ASA or WRS). Capsaicin deactiva-tion of sensory nerves aggravated mucosal lesions induced by all three ulcerogens and this effect was accompanied by a marked decrease in GBF. In such capsaicin-deactivated rats, topical capsaicin also reduced ethanol-, ASA- or WRS-induced lesions, while parenteral capsaicin was effective only in the protection against the damage induced by acidified ASA and WRS but not by ethanol. The protection against WRS lesions and accompanying rise in GBF by parenteral capsaicin were also reversed by the pretreatment with indomethacin applied in a dose suppressing the generation of PG. We conclude that capsaicin is capable of protecting gastric mucosa in rats with both intact and capsaicin-deactivated rats and that this protective activity depends, at least in part, upon its hyperemic and antisecretory effects that may be mediated, at least in part, by endogenous release of PG.

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“…The peripheral action of capsaicin is a dose-dependent action (Szolcsányi 1984;Mózsik et al 2001) (Table 9.5). Capsaicin releases CGRP and SP (Inui et al 1991;Dömötör et al 2005), which modifies the vascular reactions in the gastrointestinal mucosa (Sipos et al 2006) recently demonstrated that the existence of neuroimmune link between the CGRP, SP, and immune cells in the gastric mucosa of patients with chronic gastritis. Dömötör et al (2006b) demonstrated the increased release of glucagon during a sugar loading test in healthy human subjects, indicated a new step of capsaicin-induced changes taking place between the capsaicin-sensitive afferent nerves and neurohormonal regulation.…”

Section: Capsaicin-sensitive Afferentation In Patients Withmentioning

confidence: 99%

Capsaicin as New Orally Applicable Gastroprotective and Therapeutic Drug Alone or in Combination with Nonsteroidal Anti-Inflammatory Drugs in Healthy Human Subjects and in Patients

Mózsik

2014

Capsaicin as a Therapeutic Molecule

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Background: Capsaicin is a specific compound acting on capsaicin-sensitive afferent nerves. Aim: Capsaicin was used to study the different events of human gastrointestinal physiology, pathology, and clinical pharmacology, and possible therapeutic approaches to enhance gastrointestinal mucosal defense in healthy human subjects and in patients with various different gastrointestinal disorders as well as its use with nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy subjects and in patients. Materials and Methods: The observations were carried out in 198 healthy human subjects and in 178 patients with different gastrointestinal (GI) diseases (gastritis, erosions, ulcer, polyps, cancer, inflammatory bowel diseases, colorectal polyps, cancers), and in 69 patients with chronic (Helicobacter pylori positive and negative) gastritis (before and after eradication treatment). The gastric secretory responses and their chemical composition, gastric emptying, sugar loading test, gastric transmucosal potential difference (GTPD) with application of capsaicin alone, after ethanol alone and with capsaicin, indomethacin-induced gastric mucosal microbleeding without and with capsaicin were studied. The immunohistochemical examinations of the capsaicin receptor (TRVP1), calcitonin gene-related peptide (CGRP), and substance P (SP) were carried out in gastrointestinal tract, and especially in patients with chronic gastritis (with and without Helicobacter infection, before and after classical eradication treatment). Classical molecular pharmacological methods were applied to study the drugs inhibiting the gastric basal acid output. Results: Capsaicin decreased the gastric basal output, enhanced the "non-parietal" (buffering) component of gastric secretory responses, and gastric emptying, and the release of glucagon. Capsaicin

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Linkage between capsaicin-stimulated calcitonin gene-related peptide and somatostatin release in rat stomach

Cited by 27 publications

References 0 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

Role of Capsaicin-Sensitive Sensory Nerves in Gastroprotection against Acid-Independent and Acid-Dependent Ulcerogens

Capsaicin as New Orally Applicable Gastroprotective and Therapeutic Drug Alone or in Combination with Nonsteroidal Anti-Inflammatory Drugs in Healthy Human Subjects and in Patients

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