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Substance P (NK(1)) receptor expression by human colonic epithelial cell line Caco-2
1Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Rostock, Schillingallee 70, 18055 Rostock, Germany. sabine.boeckmann@med.uni-rostock.de
Peptides
|October 18, 2002
Summary
This study demonstrates the presence of a functional tachykinin NK(1) receptor in human Caco-2 colon cells, influencing mitogen-activated protein kinases (MAPKs) signaling pathways.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Signaling
Background:
- Substance P (SP) regulates colonic mucosal secretion.
- The expression of functional tachykinin NK(1) receptors in human colonic epithelial cells remains unclear.
Purpose of the Study:
- To investigate the expression of NK(1) receptors in human colonic epithelial cells.
- To characterize the intracellular signaling mechanisms of SP in Caco-2 cells.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) to detect NK(1) receptor transcripts.
- Fura-2 AM assay for intracellular calcium concentration.
- Mitogen-activated protein kinases (MAPKs) activity assays.
Main Results:
- NK(1) receptor transcripts were detected in Caco-2 cells.
- SP activated MAPKs in a time- and dose-dependent manner.
- A peptide NK(1) receptor antagonist acted as an agonist, while a nonpeptide antagonist blocked SP and peptide antagonist effects on MAPKs.
Conclusions:
- This study provides the first evidence of a functional NK(1) receptor in the human Caco-2 colon cell line.
- In Caco-2 cells, the peptide antagonist [D-Pro(2), D-Trp(7,9)]SP functions as an NK(1) receptor agonist, unlike the nonpeptide antagonist CP-96,345.