Phospholipase C-induced anion secretion and its interaction with carbachol in the rat colonic mucosa.
Phospholipase C (PLC) from clostridium perfringens induced a biphasic increase in short-circuit current (Isc) in the rat colon. The Isc rose rapidly to a transient peak, before it increased again to a plateau lasting for several hours. Ion replacement experiments and sensitivity to furosemide or a Cl- channel blocker indicated that PLC induced Cl- secretion. The first peak was suppressed by indomethacin, indicating mediation by prostaglandins. In contrast, the second phase was only partially sensitive to the cyclooxygenase blocker. The long-time action of PLC was dependent on intra- and extracellular Ca2+, although PLC did not induce an increase in the intracellular Ca2+ concentration of the enterocytes. The effect of PLC was blocked by the protein kinase inhibitor, staurosporine. Carbachol, when added during the second phase of the PLC response, induced a 'paradox' change in Isc: a rapid, transient increase in Isc was followed by a long-lasting decrease. This inhibition of the PLC response was more pronounced after elevation of the external Ca2+ concentration. A Ca2+ ionophore, ionomycin, and a Ca2+ channel activator, BAY K 8644, also inhibited the PLC response. The results suggest dual dependence of the action of PLC on the intracellular Ca2+ concentration.
Diener
M
M
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, F.R.G.
Eglème
C
C
Rummel
W
W
D000818:Animals; D000838:Anions; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007700:Kinetics; D010741:Phospholipases A / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology*
D000838:Anions; D002712:Chlorides; D016718:Arachidonic Acid; D002217:Carbachol; D010741:Phospholipases A; D010738:Type C Phospholipases; D002118:Calcium