The contractile action of platelet-activating factor on gallbladder smoothmuscle

Platelet-activating factor (PAF) may be a mediator of some sequelae of chol ecystitis, a disorder with gallbladder motor dysfunction. The aims of this study were to determine the effect and mechanism of PAF on gallbladder musc le. Exogenous administration of PAF-16 or PAF-18 caused dose-dependent cont ractions of gallbladder muscle strips in vitro with threshold doses of 1 ng /ml and 10 ng/ml, respectively. The PAF-induced contractions were not signi ficantly reduced by TTX, atropine, or hexamethonium but were significantly inhibited with the PAF receptor antagonists ginkolide B and CV-3988. The PA F-induced contraction was reduced by indomethacin. Preventing influx of ext racellular calcium with a calcium-free solution nearly abolished the PAF co ntractile response. Nifedipine inhibited the PAF contractile response, wher eas ryanodine had no effect. Pertussis toxin reduced the PAF contractile re sponse. In conclusion, PAF causes gallbladder contraction through specific PAF receptors on gallbladder muscle. These PAF receptors appear to be linke d to a prostaglandin-mediated mechanism and to pertussis toxin-sensitive G proteins. The contractile response is largely mediated through the utilizat ion of extracellular calcium influx through voltage-dependent calcium chann els.