Mechanisms of platelet-activating factor-induced electrolyte transport in the rat jejunum.
Platelet-activating factor (PAF) is known to cause chloride secretion in the small and large intestine in vitro. The present study investigated the mechanism of action of PAF-induced electrolyte transport in stripped rat jejunal segments mounted in standard Ussing chambers. Short circuit current was monitored as the indicator of active transport. PAF caused a concentration-dependent increase in short circuit current, whereas its precursor, lyso-PAF, did not. The response to 0.2 microM PAF was inhibited by 92% when chloride ion in the bathing solution was replaced. The response was also significantly inhibited by the PAF receptor antagonist, WEB 2170, the cyclooxygenase inhibitor, indomethacin, the phospholipase A2 inhibitor, mepacrine, and the calcium channel blocker, verapamil. In other in vitro experiments, PAF was shown to stimulate jejunal synthesis of prostaglandin E2, but not 6-keto-prostaglandin F1 alpha or the peptidoleukotrienes C4, D4 or E4. In similar experiments, 0.2 microM PAF enhanced the depletion of jejunal mucosal free arachidonic acid as measured by gas chromatography. These results show that platelet-activating factor stimulates chloride transport in the rat jejunum in vitro, and that the response is dependent upon extracellular calcium, the stimulation of phospholipase A2 and the cyclo-oxygenase catalyzed metabolism of arachidonic acid to prostaglandin E2.
MacNaughton
W K
WK
University of Calgary, Alberta, Canada.
Gall
D G
DG
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology; D001693:Biological Transport, Active; D002712:Chlorides / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004537:Eicosanoic Acids / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D014230:Triazoles / Q000494:pharmacology
D001095:Arachidonic Acids; D001381:Azepines; D002712:Chlorides; D004537:Eicosanoic Acids; D010972:Platelet Activating Factor; D014230:Triazoles; C063964:bepafant; D011796:Quinacrine; D015232:Dinoprostone; D007213:Indomethacin