BACKGROUND AND PURPOSE: ATP plays an important role as intercellular messenger acting via different types of purinergic receptors. Whereas most of the actions of ATP at intestinal epithelia are thought to be mediated by metabotropic P2Y receptors, the role of ionotropic P2X receptors remains unclear. Consequently, we investigated the role of P2X(4) and P2X(7) receptors on ion transport across rat colonic epithelia by using BzATP, a potent agonist at P2X(7) (and weak agonist at P2X(4) ). EXPERIMENTAL APPROACH: Ussing chamber and Ca(2+) imaging experiments were performed at rat colonic epithelia combined with P2X receptor expression studies. KEY RESULTS: Ussing chamber experiments revealed that serosal BzATP induced a neuronally mediated increase in short-circuit current caused by secretion of Cl(-) . In contrast, the effect of mucosal BzATP was smaller, insensitive to tetrodotoxin and Cl(-) -independent. When epithelia were basolaterally depolarized to measure currents across the apical membrane, BzATP stimulated a cation current consistent with the activation of apical nonselective cation channels. Experiments with isolated colonic crypts revealed a BzATP-induced increase in the cytosolic Ca(2+) concentration. Sensitivity to antagonists indicates stimulation of P2X(4) and P2X(7) receptors by serosal BzATP and of P2X(7) receptors by mucosal BzATP. A similar pattern was observed with native ATP which induced larger transepithelial currents in comparison to BzATP. RT-PCR and immunohistochemistry experiments confirmed the expression of P2X(4) and P2X(7) receptors in the colon localized in the epithelium and in submucosal ganglia. CONCLUSIONS AND IMPLICATIONS: Epithelial and neuronal ionotropic P2X receptors are involved in the regulation of intestinal ion transport.
- Ballout, J.
- Claßen, R.
- Richter, K.
- Grau, V.
- Diener, M.
Keywords
- Atp
- P2X receptors
- epithelium
- intestine
- ion transport
- rat
