Journal article

A Novel Antagonist Peptide Reveals a Physiological Role of Insulin-Like Peptide 5 in Control of Colorectal Function

Ruslan Pustovit, Xiaozhou Zhang, Jamie JM Liew, Praveen Praveen, Mengjie Liu, Ada Koo, Lalita Oparija-Rogenmozere, Qinghao Ou, Martina Kocan, Shuai Nie, Ross AD Bathgate, John B Furness, Mohammed Akhter Hossain

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE | AMER CHEMICAL SOC | Published : 2021

Abstract

Insulin-like peptide 5 (INSL5), the natural ligand for the relaxin family peptide receptor 4 (RXFP4), is a gut hormone that is exclusively produced by colonic L-cells. We have recently developed an analogue of INSL5, INSL5-A13, that acts as an RXFP4 agonist in vitro and stimulates colorectal propulsion in wild-type mice but not in RXFP4-knockout mice. These results suggest that INSL5 may have a physiological role in the control of colorectal motility. To investigate this possibility, in this study we designed and developed a novel INSL5 analogue, INSL5-A13NR. This compound is a potent antagonist, without significant agonist activity, in two in vitro assays. We report here for the first time ..

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Grants

Awarded by NHMRC


Awarded by Swiss National Science Foundation Early Postdoc. Mobility Fellowship


Funding Acknowledgements

These studies were supported by an NHMRC ideas grant (APP1182996) to M.A.H. and R.P. and an NHMRC project grant (APP1145686) to J.B.F. R.A.D.B. is the recipient of an NHMRC Research Fellowship (APP1135837). L.O.-R. was supported by a Swiss National Science Foundation Early Postdoc. Mobility Fellowship (P2ZHP3_187739). Studies at the Florey Institute were supported by the Victorian Government's Operational Infrastructure Support Program.