2. Academic Validation
  3. The Transient Receptor Potential Vanilloid 4 Agonist RN-1747 Inhibits the Calcium Response to Histamine

The Transient Receptor Potential Vanilloid 4 Agonist RN-1747 Inhibits the Calcium Response to Histamine

  • Pharmacology. 2019;104(3-4):166-172. doi: 10.1159/000501144.
Beatrix Pfanzagl 1,  Roswitha Pfragner 2,  Erika Jensen-Jarolim 3 4
Affiliations

Affiliations

  • 1 Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria, [email protected].
  • 2 Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.
  • 3 Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
  • 4 The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
PMID: 31212298 DOI: 10.1159/000501144
Abstract

Background: Sensitization of transient receptor potential (TRP) cation channels probably contributes to intestinal hypersensitivity, a hallmark of gastrointestinal disorders. Histamine acting via histamine 1 receptor (H1R) to open TRP cation channels might also be involved.

Method: The enterochromaffin cell line P-STS, responsive to histamine via H1R, was used as model to study possible synergism between histamine and TRP vanilloid 4 (TRPV4) pathways.

Results: The TRPV4 antagonist RN-1734, but not HC-067047, inhibited the cytoplasmic calcium response to histamine in P-STS cells. However, also pre-incubation with the TRPV4 agonist RN-1747 strongly inhibited the calcium response to histamine in P-STS as well as HeLa cells. This inhibitory effect of RN-1747 was not due to its known TRP melastatin 8 (TRPM8) antagonism, as the TRPM8 antagonist RQ-00203078 showed no significant effect on the histamine-induced calcium response of P-STS or HeLa cells.

Conclusion: The TRPV4 agonist RN-1747, and possibly also the structurally similar TRPV4 antagonist RN-1734, should be used with caution because of yet unidentified interference with histamine signaling via H1R.

Keywords

Histamine; Irritable bowel disease; Phenylsulfonamide; RN-1747; Transient receptor potential vanilloid 4.

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