Evidence that Ca2+ fluxes and respiratory, glycogenolytic and vasoconstrictive effects induced by the action of platelet-activating factor and L-alpha-lysophosphatidylcholine in the perfused rat liver are mediated by products of the cyclo-oxygenase pathway.
The administration of 'acetylglyceryl ether phosphorylcholine' (AGEPC, also known as platelet-activating factor) and L-alpha-lysophosphatidylcholine (LPC) to rat livers perfused with media containing 1.3 mM-Ca2+ was followed by a concentration-dependent efflux of Ca2+ from the liver. Near-maximal response was observed at 100 nM-AGEPC and 50 microM-LPC, and resulted in a net efflux of approx. 130 nmol of Ca2+/g of liver. Onset of Ca2+ efflux occurred about 10 s after AGEPC and LPC administration, reached a maximum after about 50 s (the maximum rate of efflux was approx. 180 nmol/min per g) and thereafter decreased rapidly, and was sometimes followed by a much smaller influx of Ca2+. Sequential infusions of AGEPC or LPC, and phenylephrine, indicate that each of these agents mobilizes Ca2+ from the same intracellular source. The efflux of Ca2+ was not observed in the presence of indomethacin or bromophenacyl bromide, or when the liver was perfused with low-Ca2+-containing (25 microM) media. Other physiological responses, such as changes in respiration, glucose output and portal pressure, were also inhibited under these conditions. The results suggest that the Ca2+-flux changes and other responses are mediated by prostaglandins produced and released within the liver, possibly by cell types other than hepatocytes.
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000098:Acetophenones; D008112:Liver Glycogen; D008244:Lysophosphatidylcholines; D010972:Platelet Activating Factor; D011451:Prostaglandin-Endoperoxide Synthases; C006821:4-bromophenacyl bromide; D002118:Calcium; D007213:Indomethacin