Journal article

Publication year: 2008

Pages: 156-163

Journal: European Journal of Pharmacology

Volume number: 583

Issue number: 1

ISSN: 0014-2999

DOI Link: https://doi.org/10.1016/j.ejphar.2008.01.017

Publisher: Elsevier

Abstract: 

Stimulation of muscarinic receptors is known to have a biphasic effect on colonic Cl- secretion: a short-lasting activation, which is followed by a long-lasting inhibition. In order to find out, which role G(q) proteins play in both processes, Pasteurella multocida toxin was used, a known activator of G alpha(q). This toxin (1.5 mu g/ml) had a dual action on short-circuit current (I-sc) across rat distal colon: it stimulated transiently I-sc and subsequently down-regulated the I-sc evoked by Ca2+-dependent secretagogues such as acetylcholine or ATP. The inactive mutant (P. multocida toxin C1165S), which does not stimulate G(q)(alpha) was ineffective. Cl- dependence and sensitivity against bumetanide, a blocker of the Na+-K+-2Cl(-) cotransporter, confirmed that the increase in I-sc evoked by the toxin represented Cl- secretion. The effect of P multocida toxin was suppressed by YM-254890 (10(-7) M), a blocker of G(q)(alpha), Experiments with apically permeabilized tissues revealed that the secretory response to P. multocida toxin was concomitant with an increase in basolateral K+ conductance as it is observed for other agonists inducing Ca2+-dependent anion secretion. Consequently, these results suggest that G(q) proteins are not only involved in the activation of secretion, e.g. after stimulation of muscarinic or purinergic receptors, but also play a central role in the long-term down-regulation of intestinal secretion after activation of these types of receptors.

Harvard Citation style: Hennig, B., Orth, J., Aktories, K. and Diener, M. (2008) Anion secretion evoked by Pasteurella multocida toxin across rat colon, European Journal of Pharmacology, 583(1), pp. 156-163. https://doi.org/10.1016/j.ejphar.2008.01.017

APA Citation style: Hennig, B., Orth, J., Aktories, K., & Diener, M. (2008). Anion secretion evoked by Pasteurella multocida toxin across rat colon. European Journal of Pharmacology. 583(1), 156-163. https://doi.org/10.1016/j.ejphar.2008.01.017