Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01

Naitou, K., Mamerto, T.P., Pustovit, R.V., Callaghan, B., Rivera, L.R., Chan, A.J., Ringuet, M.T., Pietra, C. and Furness, J.B. 2015, Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01, Neurogastroenterology & motility, vol. 27, no. 12, pp. 1764-1771, doi: 10.1111/nmo.12688.

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Title Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01
Author(s) Naitou, K.
Mamerto, T.P.
Pustovit, R.V.
Callaghan, B.
Rivera, L.R.
Chan, A.J.
Ringuet, M.T.
Pietra, C.
Furness, J.B.
Journal name Neurogastroenterology & motility
Volume number 27
Issue number 12
Start page 1764
End page 1771
Total pages 8
Publisher Wiley-Blackwell
Place of publication Chichester, Eng.
Publication date 2015-12
ISSN 1350-1925
Keyword(s) defecation
ghrelin receptors
Summary Background It has been recently demonstrated that the ghrelin receptor agonist, HM01, caused defecation in rats that were treated to provide a model for the constipation of Parkinson's disease. HM01 significantly increased fecal output and increased Fos activity in neurons of the hypothalamus and hindbrain, but not in the spinal defecation center. Other ghrelin agonists act on the defecation center. Methods Receptor pharmacology was examined in ghrelin receptor (GHSR1a) transfected cells. Anesthetized rats were used to investigate sites and mechanisms of action. Key Results HM01 activated rat GHSR1a at nanomolar concentrations and was antagonized by the GHSR1a antagonist, YIL781. HM01, intravenous, was potent to activate propulsive colorectal contractions. This was prevented by pelvic nerve section and by intravenous YIL781, but not by spinal cord section rostral to the defecation centers. Direct intrathecal application of HM01 to the defecation center at spinal level L6-S1 initiated propulsive contractions of the colorectum. Conclusions & Inferences HM01 stimulates GHSR1a receptors on neurons in the lumbosacral defecation centers to cause propulsive contractions and emptying of the colorectum. It has greater potency when given systemically, compared with other GHSR1a agonists.
Language eng
DOI 10.1111/nmo.12688
Field of Research 110399 Clinical Sciences not elsewhere classified
1103 Clinical Sciences
1109 Neurosciences
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Grant ID NHMRC 1005811
Copyright notice ©2015, John Wiley & Sons
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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