The gut hormone, ghrelin, its pharmacology, and the possible application of ghrelin receptor agonists in therapy
|Professor John B Furnessfirstname.lastname@example.org||View page|
Ghrelin is a hormone released from gastric endocrine cells. However, ghrelin receptors occur at other sites, notably in the central nervous system and in tumour cells. Our focus has been on ghrelin receptors in the lumbosacral defecation centres and in breast cancer cells. In the defecation centres, centrally penetrant ghrelin receptor agonists are very effective stimulants, but we have proven that ghrelin itself does not act at this site. One of our aims is to determine what is the natural stimulus for the activation of these receptors.
In breast cancer, we have discovered that ghrelin and ghrelin related peptides are suppressors of proliferation of human breast cancer cells. The receptor type involved is unknown. We are investigating whether it would be possible to use ghrelin-related agonists in the treatment of breast cancers.
Dr Ruslan Pustovit
Dr Brid Callaghan
Dr Kristy Brown
- Au CC, Furness JB, Brown KA. Ghrelin and breast cancer: emerging roles in obesity, estrogen regulation, and cancer. Frontiers in Oncology 2017; 6(265): 1-7. doi: 10. 3389/fonc.2016.00265.
- Au CC, Docanto MM, Zahid H, Raffaelli FM, Ferrero RL, Furness JB, Brown KA. Des-acyl ghrelin inhibits the capacity of macrophages to stimulate the expression of aromatase in breast adipose stromal cells. J Steroid Biochem Mol Biol 2016 Jul 14; doi: 10.1016/j.jsbmb.2016.07.005.
- Sanger GJ, Furness JB. Ghrelin and motilin receptors as drug targets for gastrointestinal disorders. Nature Rev Gastroenterol Hepatol 2017; 19: 38-48.
- Ellis AG, Zeglinski PT, Brown DJ, Frauman AG, Millard M, Furness JB. Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose phase 1 safety trial in spinal cord injured and able bodied volunteers. Spinal Cord 2015; 53: 103-108.
- Naitou K, Mamerto TP, Pustovit RV, Callaghan B, Rivera LR, Chan AJ, Ringuet MT, Pietra C, Furness JB. Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01. Neurogastroenterol Motil 2015; 27: 1596-1603.
- Pustovit RV, Furness JB, Rivera LR. A ghrelin receptor agonist is an effective colokinetic in rats with diet induced constipation. Neurogastroenterol Motil 2015; 27: 610-617.
- Callaghan B, Furness JB. Novel and conventional receptors for ghrelin, desacyl-ghrelin and pharmacologically related compounds. Pharmacol Rev 2014; 66: 984-1001.
- Docanto, MM, Yang, F, Callaghan, B, Ragavan, R, Wang, X, Furness, JB, Andrews, ZB, Brown, KA: Ghrelin and des-acyl ghrelin inhibit aromatase expression and activity in human adipose stromal cells: suppression of cAMP as a possible mechanism. Breast Cancer Research and Treatment 2014; 147: 193-201.
- Pustovit RV, Callaghan B, Kosari, Rivera LR, Thomas H, Brock JA, Furness JB. The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin. Neurogastroenterol Motil 2014; 26: 264-271.
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