Anion secretion evoked by Pasteurella multocida toxin across rat colon.
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 Gq proteins play in both processes, Pasteurella multocida toxin was used, a known activator of G alpha q. This toxin (1.5 microg/ml) had a dual action on short-circuit current (Isc) across rat distal colon: it stimulated transiently Isc and subsequently down-regulated the Isc evoked by Ca2+-dependent secretagogues such as acetylcholine or ATP. The inactive mutant (P. multocida toxin C1165S), which does not stimulate G alpha q), was ineffective. Cl(-) dependence and sensitivity against bumetanide, a blocker of the Na+-K+-2Cl(-) cotransporter, confirmed that the increase in Isc 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 alpha q. 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 Gq 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.
Hennig
Britta
B
Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, D-35392 Giessen, Germany.
Orth
Joachim
J
Aktories
Klaus
K
Diener
Martin
M
D000109:Acetylcholine / Q000494:pharmacology; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D000838:Anions; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002712:Chlorides; D018721:Muscarinic Agonists; C062258:Pasteurella multocida toxin; D010456:Peptides, Cyclic; C475455:YM-254890; D000255:Adenosine Triphosphate; D002217:Carbachol; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D000109:Acetylcholine; D002118:Calcium; D007213:Indomethacin