Ghrelin and gastric acid secretion

Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

doi:10.3748/wjg.14.6334

Cited by 43 publications

(17 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Difference in exercise protocols and intensities might explain these discrepancies. Nevertheless, these changes remained after vagotomy, suggesting that secretion of ghrelin and PYY might be partially mediated or not mediated by vagal nerves (Inui et al 2004;Hosoda and Kangawa 2008;Yakabi et al 2008).…”

Section: Fig 3 Antral and Duodenal Motilities In The Vagotomized Ramentioning

confidence: 99%

Vagal Nerve Regulation Is Essential for the Increase in Gastric Motility in Response to Mild Exercise

Wang

Kondo

Suzukamo

et al. 2010

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

It has been shown that mild to moderate exercise can accelerate gastric emptying in humans. However, understanding of the underlying mechanism is hampered by the lack of appropriate animal models. To investigate the effects of mild exercise on gastric motility, we developed an animal model, in which strain gauge transducers were surgically planted on the antral surfaces of female Sprague-Dawley rats. We continuously recorded the contractions of gastric circular muscle in unrestrained conscious rats, divided into four groups: sham-operated exercise, sham-operated sedentary, vagotomized exercise, and vagotomized sedentary. The rats were trained for 3 weeks, and gastric motility was monitored before and after exercise. Although exercise accelerates gastric antral contraction in sham-operated rats, this effect was absent in the vagotomized exercise group, indicating the involvement of the vagal nerve in the exercise-mediated increase in gastric motility. Among the four groups, daily food intake was highest in the sham-operated exercise group. In contrast, the vagotomized exercise group exhibited the smallest body weight gain. Severe gastric retention was observed in vagotomized rats, suggesting a role of the vagal nerve in facilitating food movement and digestion in the stomach. Moreover, at the end of the 3-week exercise, there were no differences in plasma levels of growth hormone, peptid YY, and ghrelin among the four groups. These results indicate that in response to a mild physical exercise challenge, the vagal nerve stimulates gastric motility and enhances the ability of the stomach to process food. Our findings highlight the significance of neuronal control of stomach function.

show abstract

Section: Fig 3 Antral and Duodenal Motilities In The Vagotomized Ramentioning

confidence: 99%

Vagal Nerve Regulation Is Essential for the Increase in Gastric Motility in Response to Mild Exercise

Wang

Kondo

Suzukamo

et al. 2010

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…Selective blockade of the gastric vagus nerve either by capsaicin (afferent only) or surgical differentiation (afferent and efferent pathways) blocks c-Fos expression within the arcuate nucleus in response to ghrelin-induced feeding. Vagotomy also eliminates ghrelininduced growth hormone secretion indicating a novel vagus-mediated growth hormone secretion pathway [35], in addition to the known vagus-mediated efferent regulation of gastrointestinal motility, gastric acid secretion and nausea [53][54][55].…”

Section: Introductionmentioning

confidence: 98%

Pharmacokinetics and pharmacodynamics of PF‐05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects

Denney

Sonnenberg

Carvajal‐Gonzalez

et al. 2016

Brit J Clinical Pharma

View full text Add to dashboard Cite

AIMTo evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults. METHODSSingle (SAD) and multiple ascending dose (MAD) studies were randomised, placebo-controlled, double-blind studies. Thirty-five healthy men (age 38.2 ± 10.4 years; body mass index 24.8 ± 3.1 kg m -2 [mean ± standard deviation]) received ≥1 dose (2, 10, 40 [divided], 50, 100, 150, and 300 [single or divided] mg) of PF-05190457 and/or placebo in the SAD. In the MAD study, 35 healthy men (age 39.7 ± 10.1 years; body mass index 25.9 ± 3.3 kg m -2 ) received ≥1 dose (2, 10, 40 and 100 mg twice daily) of PF-05190457 and/or placebo daily for 2 weeks. RESULTSPF-05190457 absorption was rapid with a T max of 0.5-3 hours and a half-life between 8.2-9.8 hours. PF-05190457 dosedependently blocked ghrelin (1 pmol kg -1 min -1 )-induced growth hormone (GH) release with (mean [90% confidence interval]) 77% [63-85%] inhibition at 100 mg. PF-05190457 (150 mg) delayed gastric emptying lag time by 30% [7-58%] and half emptying time by 20% [7-35%] with a corresponding decrease in postprandial glucose by 9 mg dL -1 . The most frequent adverse event reported by 30 subjects at doses ≥50 mg was somnolence. PF-05190457 plasma concentrations also increased heart rate up to 13.4 [4.8-58.2] beats min -1 and, similar to the effect on glucose and ghrelin-induced GH, was lost within 2 weeks. CONCLUSIONSPF-05190457 is a well-tolerated first-in-class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing. Blocking ghrelin receptors inhibits ghrelin-induced GH, and increases heart rate, effects that underwent tachyphylaxis with chronic dosing. PF-051940457 has the potential to treat centrally-acting disorders such as insomnia. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• PF-05190457 is a selective inverse agonist of the ghrelin receptor with a nonclinical profile supporting human dosing.• Endogenous ghrelin and exogenous infusions in healthy subjects release growth hormone, stimulate hunger and increases gastric motility WHAT THIS STUDY ADDS• PF-05190457 is the first reported ghrelin receptor inverse agonist profiled in humans. It is safe and well-tolerated in healthy subjects with pharmacokinetics supporting daily oral dosing.• PF-05190457 blocks ghrelin receptors in healthy subjects, dose-dependently increases heart rate, delays gastric emptying, induces somnolence and maximal inhibition for 2 weeks yields tachyphylaxis. Tables of Links IntroductionGhrelin is an endogenous 28-amino acid acylated peptide synthesised within the stomach fundus associated with modulating growth hormone secretion, gastric motility, gastric acid secretion and hunger. Acylated ghrelin is the only peripheral hunger-stimulating hormone that elevates preprandially in plasma, suggesting a role in meal initiation in humans [3]. Circulating endogenous baseline and pulsatile patterns of total ghrelin are inhibited in obese subjects following gastric bypass surgery [4,5]; however, not all studies ha...

show abstract

“…It is involved in different physiological and pathological responses, such as the immune response, gastric acid secretion, neurotransmission and angiogenesis (Brimble and Wallis, 1973; Akdis and Simons, 2006; Hegyesi et al. , 2008; Yakabi et al. , 2008; Zampeli and Tiligada, 2009).…”

Section: Introductionmentioning

confidence: 99%

Histamine modulates γδ‐T lymphocyte migration and cytotoxicity, via G_i and G_s protein‐coupled signalling pathways

Truta-Feles

Lagadari

Lehmann

et al. 2010

British J Pharmacology

View full text Add to dashboard Cite

Background and purpose:The biogenic amine, histamine plays a pathophysiological regulatory role in cellular processes of a variety of immune cells. This work analyses the actions of histamine on gd-T lymphocytes, isolated from human peripheral blood, which are critically involved in immunological surveillance of tumours. Experimental approach: We have analysed effects of histamine on the intracellular calcium, actin reorganization, migratory response and the interaction of human gd T cells with tumour cells such as the A2058 human melanoma cell line, the human Burkitt's Non-Hodgkin lymphoma cell line Raji, the T-lymphoblastic lymphoma cell line Jurkat and the natural killer cell-sensitive erythroleukaemia cell line, K562. Key results: gd T lymphocytes express mRNA for different histamine receptor subtypes. In human peripheral blood gd T cells, histamine stimulated Pertussis toxin-sensitive intracellular calcium increase, actin polymerization and chemotaxis. However, histamine inhibited the spontaneous cytolytic activity of gd T cells towards several tumour cell lines in a cholera toxin-sensitive manner. A histamine H4 receptor antagonist abolished the histamine induced gd T cell migratory response. A histamine H2 receptor agonist inhibited gd T cell-mediated cytotoxicity. Conclusions and implications:Histamine activated signalling pathways typical of chemotaxis (Gi protein-dependent actin reorganization, increase of intracellular calcium) and induced migratory responses in gd T lymphocytes, via the H4 receptor, whereas it down-regulated gd T cell mediated cytotoxicity through H2 receptors and Gs protein-coupled signalling. Our data suggest that histamine activated gd T cells could modulate immunological surveillance of tumour tissue. Linked articles:This article is part of a themed section on Analytical Receptor Pharmacology in Drug Discovery. To view the other articles in this section visit http://dx

show abstract

Ghrelin and gastric acid secretion

Cited by 43 publications

References 37 publications

Vagal Nerve Regulation Is Essential for the Increase in Gastric Motility in Response to Mild Exercise

Vagal Nerve Regulation Is Essential for the Increase in Gastric Motility in Response to Mild Exercise

Pharmacokinetics and pharmacodynamics of PF‐05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects

Histamine modulates γδ‐T lymphocyte migration and cytotoxicity, via G_i and G_s protein‐coupled signalling pathways

Contact Info

Product

Resources

About

Ghrelin and gastric acid secretion

Cited by 43 publications

References 37 publications

Vagal Nerve Regulation Is Essential for the Increase in Gastric Motility in Response to Mild Exercise

Vagal Nerve Regulation Is Essential for the Increase in Gastric Motility in Response to Mild Exercise

Pharmacokinetics and pharmacodynamics of PF‐05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects

Histamine modulates γδ‐T lymphocyte migration and cytotoxicity, via Gi and Gs protein‐coupled signalling pathways

Contact Info

Product

Resources

About

Histamine modulates γδ‐T lymphocyte migration and cytotoxicity, via G_i and G_s protein‐coupled signalling pathways