PAF-like lipids- and PAF-induced gallbladder muscle contraction is mediated by different pathways in guinea pigs.
H2O2 stimulates gallbladder muscle contraction and scavengers of free radicals through the generation of PGE2. Oxidative stress causes lipid peroxidation and generation of platelet-activating factor (PAF) or PAF-like lipids. The present studies therefore were aimed at determining whether either one induced by H2O2 mediates the increased generation of PGE2. Dissociated muscle cells of guinea pig gallbladder were obtained by enzymatic digestion. Both PAF-like lipids and PAF-induced muscle contraction was blocked by the PAF receptor antagonist CV-3988. This antagonist also blocked the increased PGE2 production caused by PAF-like lipids or PAF. Actions of PAF-like lipids were completely inhibited by indomethacin, but those of PAF were only partially reduced by indomethacin or by nordihydroguaiaretic acid and completely blocked by their combination. PAF-like lipids-induced contraction was inhibited by AACOCF3 (cystolic phospholipase A2 inhibitor), whereas the actions of PAF were blocked by MJ33 (secretory phospholipase A2 inhibitor). Receptor protection studies showed that pretreatment with PAF-like lipids before N-ethylmaleimide protected the contraction induced by a second dose of PAF-like lipids or PGE2 but not by PAF. In contrast, pretreatment with PAF protected the actions of PAF and PGE2 but not that of PAF-like lipids. Both PAF-like lipids and PAF-induced contractions were inhibited by anti-Galphaq/11 antibody and by inhibitors of MAPK and PKC. In conclusion, PAF-like lipids seem to activate a pathway different from that of PAF probably by stimulating a different PAF receptor subtype.
Guarino
Michele P L
MP
Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.
Xiao
Zuo-Liang
ZL
Biancani
Piero
P
Behar
Jose
J
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050356:Lipid Metabolism; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology
D016877:Oxidants; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D006861:Hydrogen Peroxide; D015232:Dinoprostone