Identification and characterization of a novel gastric peptide hormone: The motilin-related peptide

Tomasetto, Catherine; Karam, Sherif M.; Ribieras, Stéphane; Masson, Régis; Lefèbvre, Olivier; Staub, Adrien; Alexander, Glory; Chenard, Marie–Pierre; Rio, Marie‐Christine

doi:10.1053/gast.2000.9371

Cited by 214 publications

(129 citation statements)

References 28 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…Such acylation is thought to be critical for transport across the blood-brain barrier, receptor binding and overall bioactivity (Muccioli et al 2001, Banks et al 2002. The major site of ghrelin production is the stomach mucosa (Date et al 2000, Tomasetto et al 2000, Rindi et al 2002, whereas lower amounts derive from small and large intestine, pancreas, kidney, immune system, placenta, pituitary, testis, ovary and hypothalamus (Casanueva and Dieguez 2002). With the possible exception of mouse (Tomasetto et al 2000), ghrelin cells have been demonstrated to be independent from somatostatin (D), serotonin (enterochromaffin, or EC) and histamine (enterochromaffin-like, or ECL)-producing cells (Date et al 2000, Rindi et al 2002, and comprise P/D1-type cells in human, A-like cells in rat and X cells in dog (Rindi et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Gastric immunolocalization and plasma profiles of acyl-ghrelin in fasted and fasted-refed prepuberal gilts

Govoni¹,

Iasio²,

Cocco³

et al. 2005

Journal of Endocrinology

View full text Add to dashboard Cite

Ghrelin is a peripheral circulating hormone, mainly released from the stomach, which can stimulate food intake. We studied fed, fasted and fasted-refed prepuberal gilts in order to outline possible changes in gastric mucosal ghrelin cells and in plasma ghrelin profiles in reponse to food deprivation. Acyl-ghrelin-immunoreactive cells were numerous in oxyntic glands, less abundant in cardiac glands and least frequent in pyloric glands, with the addition of a minor population of labelled cells in the gastric pit mucosa. When fed and fasted animals were compared (72-h fast versus fed; n=4 each), no clear-cut differences were revealed in labelled cell numbers, nor in their staining intensity. An RIA for plasma porcine acyl-ghrelin (noctanoylated at Ser-3), not recognizing des-acyl-ghrelin, was validated. Plasma acyl-ghrelin progressively increased upon fasting (over 6, 12, 24 and 48 h); ghrelin levels significantly (P<0·05) higher than those prefast were reached at 72 h. After refeeding, plasma ghrelin was rapidly restored to basal values by 6 h. In the same animals, plasma insulin was significantly reduced throughout the fasting period (6-72 h), while rapidly increasing after refeeding. Non-esterified fatty acid levels increased during fasting (12-72 h) and rapidly returned to low values after refeeding. In conclusion, the present study demonstrates that starvation and refeeding influence ghrelin plasma level in prepuberal gilts. The absence of detectable changes in ghrelin cells, as seen in immunohistochemistry, could be due to a large intracellular storage of potentially releasable acyl-ghrelin.

show abstract

Section: Introductionmentioning

confidence: 99%

Gastric immunolocalization and plasma profiles of acyl-ghrelin in fasted and fasted-refed prepuberal gilts

Govoni¹,

Iasio²,

Cocco³

et al. 2005

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Originally identified in 1999 as the natural ligand for the growth hormone secretagogue receptor (GHS-1a) or ghrelin receptor (GRLN-R) [19,20], ghrelin is an orexigenic hormone produced mainly in the oxyntic mucosa of the stomach [22] with significant sequence similarity to motilin [23]. It is derived from the human ghrelin gene via alternative splicing [24] and synthesized from precursor peptides that undergo post-translational processing [25].…”

Section: The Role Of Ghrelinmentioning

confidence: 99%

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

Shin

2015

Curr Gastroenterol Rep

View full text Add to dashboard Cite

There remains an unmet need for effective pharmacologic treatments for gastroparesis.Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and has been shown to regulate energy homeostasis and exert prokinetic effects on gastrointestinal motility. In recent years, several ghrelin receptor agonists have been studied in clinical trials of patients with diabetic gastroparesis. The intravenous macrocyclic peptidomimetic, TZP-101 initially suggested improvement in gastroparesis symptoms with intravenous administration when compared to placebo. However, in subsequent studies of oral preparations, TZP-102 failed to confirm these results. Another ghrelin receptor agonist, RM-131 was recently shown to significantly accelerate gastric emptying (GE) in patients with type 1 and type 2 diabetes and delayed GE. RM-131 reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) and composite scores among type 1 diabetics. Continued development of ghrelin agonists should be explored in attempts to expand therapeutic options for the treatment of gastroparesis.

show abstract

“…4% of agarose gel stained with ethidium bromide and visualized under UV light. For ghrelin, GHS-R 1a, and GHS-R 1b PCRs, positive controls included respectively a pSG5 vector containing human ghrelin cDNA (Tomasetto et al 2000), a pEGFP-N1 vector containing human GHS-R 1a cDNA (Van Craenenbroeck et al 2004), and human placenta cDNA.…”

Section: Ghrelin (And Ghrelin Receptors) Mrna Detection By Rt-pcrmentioning

confidence: 99%

Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells

Vriese

Delporte

2007

Journal of Endocrinology

View full text Add to dashboard Cite

Ghrelin is a 28 amino acid peptide hormone that is mainly produced by the stomach, but also by several tissues and tumors. Ghrelin is octanoylated on the Ser 3 , but is also detected as a des-acylated form. Only the acylated ghrelin activates the GH secretagogue receptor (GHS-R) type 1a to stimulate GH release, and regulate food intake and energy metabolism. For the first time, we report that ghrelin and des-acyl ghrelin are present in human promyelocytic HL-60, monocytic THP-1 and lymphoblastic SupT1 cell lines. The human leukemic cell lines did not express the functional GHS-R 1a, whereas they expressed GHS-R 1b, a truncated variant of the receptor. Leukemic cell proliferation was not modified by the addition of octanoylated or des-acyl ghrelins.However, THP-1 and HL-60 cell proliferations were inhibited by SB801, an antibody directed against the N-terminal octanoylated portion of ghrelin, suggesting that octanoylated ghrelin stimulates cell proliferation via an autocrine pathway involving an as yet unidentified ghrelin receptor. Both octanoylated and des-acyl ghrelins did not alter the basal adenylate cyclase activity. Treatments of THP-1 and SupT1 cells by both octanoylated and des-acyl ghrelins did not modify the adenylate cyclase activity in response to vasoactive intestinal peptide, suggesting that ghrelin is unlikely to modulate the anti-inflammatory and differentiating properties of vasoactive intestinal peptide.

show abstract

Identification and characterization of a novel gastric peptide hormone: The motilin-related peptide

Cited by 214 publications

References 28 publications

Gastric immunolocalization and plasma profiles of acyl-ghrelin in fasted and fasted-refed prepuberal gilts

Gastric immunolocalization and plasma profiles of acyl-ghrelin in fasted and fasted-refed prepuberal gilts

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells

Contact Info

Product

Resources

About