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Druce, Maralyn; Bloom, Stephen R.

doi:10.1097/00075197-200307000-00002

Cited by 42 publications

(3 citation statements)

References 78 publications

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“…Why HM01 activated the PVH and other closely associated nuclei without causing increases in c-Fos in the CeA also remains to be determined. The CeA is involved in mechanisms of food intake and is part of a higher level of circuitry in the forebrain implicated in both hedonic (pleasurable) feeding (Andrews & Rudd, 2015) and in nausea and emesis has been shown to reduce anxiety to facilitate feeding (Druce & Bloom, 2003).…”

Section: Discussionmentioning

confidence: 99%

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The brain‐penetrating, orally bioavailable, ghrelin receptor agonist HM01 ameliorates motion‐induced emesis in Suncus murinus (house musk shrew)

Ngan

et al. 2020

British J Pharmacology

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Background and Purpose HM01, a novel, orally bioavailable, brain‐penetrating agonist of ghrelin receptors, ameliorates emesis in Suncus murinus. This study compared HM01's activity against motion sickness with that of the less brain‐penetrating ghrelin receptor agonist, HM02. Experimental Approach The potential of HM01 and HM02 to relax isolated mesenteric arteries and to increase feeding was investigated. Radio telemetry was used to record gastric slow waves and body temperature. Plethysmography was used to measure respiratory function. HM01 and HM02 were administered p.o. 1 hr prior to provocative motion, and c‐Fos expression in brain sections was assessed. Key Results HM01 and HM02 both relaxed precontracted arteries, yielding EC50 values of 2.5 ± 0.5 and 3.5 ± 0.4 nM respectively. HM01 increased feeding, but HM02 did not. Both compounds caused hypothermia and bradygastria. Motion induced 123 ± 24 emetic events. HM01, but not HM02, reduced motion‐induced emesis by 67.6%. Motion increased c‐Fos expression in the nucleus tractus solitarius (NTS), dorsal motor nucleus of the vagus (DMNV), medial vestibular nucleus (MVe), central nucleus of the amygdala, and paraventricular hypothalamic nucleus (PVH). HM01 alone increased c‐Fos expression in the area postrema, NTS, DMNV, PVH, and arcuate hypothalamic nucleus; HM02 had a similar pattern except it did not increase c‐Fos in the PVH. Both compounds antagonized the motion‐induced increases in c‐Fos expression in the MVe. Conclusions and Implications HM01 is more effective than HM02 in preventing motion‐induced emesis. The difference in potency may relate to activation of ghrelin receptors in the PVH.

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Section: Discussionmentioning

confidence: 99%

“…, the 3rd ventricle; AP, area postrema; Arc, arcuate hypothalamic nucleus; DMNV, dorsal motor nucleus of vagus; NTS, nucleus tractus solitarius. Scale bar: 100 μm Stimulation of ghrelin receptors in the amygdala in other species has been shown to reduce anxiety to facilitate feeding(Druce & Bloom, 2003).…”

mentioning

confidence: 99%

The brain‐penetrating, orally bioavailable, ghrelin receptor agonist HM01 ameliorates motion‐induced emesis in Suncus murinus (house musk shrew)

Ngan

et al. 2020

British J Pharmacology

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“…Loss of appetite is one of its clinical features [14]. Appetite is under the control of cerebral functions [15,16]. Ghrelin is known as an appetite-regulating hormone [6,17].…”

Section: Discussionmentioning

confidence: 99%

Effects of Iron Deficiency Anemia and its Treatment on Ghrelins, Obestatin and Heat Shock Protein 70

Kaşar

Akarsu

Aydın

2023

Int. J. Child Health Nutr.

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The impact of iron deficiency anemia (IDA) and its treatment on increased levels of heat shock protein 70 (HSP70) in settings with higher tissue stress induced by both ghrelin, which is both an antioxidant and a food intake stimulant, and also obestatin with opposing effects were investigated. The association of pica with these parameters was also examined. The study included 28 patients with IDA and 28 healthy controls. While acyl ve des-acyl ghrelin values were lower (p<0.05) in IDA. With treatment, ghrelin levels climbed. In IDA, obestatin levels were higher than the control values (p<0.05). With the IDA treatment, acyl and des-acyl Ghrelin levels increased. Contrarily, obestatin values fell down. The concentration of HSP 70 in IDA and during its therapy was above control values. Acyl, des-acyl ghrelin, obestatin, and HSP70 levels were increased in the pica group. In the pica group obestatin/acyl ghrelin ratio was comparatively higher (p<0.05). In IDA decrease in ghrelin and an increase in obestatin levels are observed, while HSP 70 remains the same. An increase in the obestatin/acyl ghrelin ratio might be responsible for the pica disorder.

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A 9‐year‐old male with a duplication of chromosome 3p25.3p26.2: Clinical report and gene expression analysis

Bittel

Kibiryeva

Dasouki

et al. 2006

American J of Med Genetics Pt A

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We describe a 9-year-old male referred for genetic evaluation for Prader-Willi syndrome (PWS). PWS is the most common genetically-defined cause of life-threatening obesity and results from a functional loss of paternally-expressed genes from the chromosome 15q11-q13 region. The patient presented with pervasive developmental disorder, delayed speech and rapid onset of obesity at age 4 years, all features similar to PWS. However, chromosome 15q11-q13 methylation testing and fragile X studies were normal. GTG-banding and fluorescence in situ hybridization with whole chromosome 3 paint probe and a chromosome 3p subtelomeric probe suggested a duplication of 3p25.3p26.2, a finding supported by comparative genomic hybridization. This region of chromosome 3p contains genes which contribute to obesity and behavioral problems, most notably, ghrelin (GHRL), an oxytocin receptor (OXTR), solute carrier family 6 members (GABA neurotransmitter transporters, SLC6A1 and SLC6A11) and peroxisome proliferator-activated receptor, gamma (PPARG). To characterize these obesity and behavior related genes in our subject, we performed quantitative RT-PCR and compared expression levels with similarly aged male subjects (four nonobese males, four obese males and four PWS males -two with 15q11-q13 deletions and two with maternal disomy 15). Our studies suggest increased expression of several genes in the 3p duplication region, including GHRL and PPARG, which may contribute to the phenotypic features in our 3p duplication subject.

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Cited by 42 publications

References 78 publications

The brain‐penetrating, orally bioavailable, ghrelin receptor agonist HM01 ameliorates motion‐induced emesis in Suncus murinus (house musk shrew)

The brain‐penetrating, orally bioavailable, ghrelin receptor agonist HM01 ameliorates motion‐induced emesis in Suncus murinus (house musk shrew)

Effects of Iron Deficiency Anemia and its Treatment on Ghrelins, Obestatin and Heat Shock Protein 70

A 9‐year‐old male with a duplication of chromosome 3p25.3p26.2: Clinical report and gene expression analysis

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