The contractile action of platelet-activating factor on gallbladder smooth muscle.
Platelet-activating factor (PAF) may be a mediator of some sequelae of cholecystitis, a disorder with gallbladder motor dysfunction. The aims of this study were to determine the effect and mechanism of PAF on gallbladder muscle. Exogenous administration of PAF-16 or PAF-18 caused dose-dependent contractions of gallbladder muscle strips in vitro with threshold doses of 1 ng/ml and 10 ng/ml, respectively. The PAF-induced contractions were not significantly reduced by TTX, atropine, or hexamethonium but were significantly inhibited with the PAF receptor antagonists ginkolide B and CV-3988. The PAF-induced contraction was reduced by indomethacin. Preventing influx of extracellular calcium with a calcium-free solution nearly abolished the PAF contractile response. Nifedipine inhibited the PAF contractile response, whereas ryanodine had no effect. Pertussis toxin reduced the PAF contractile response. In conclusion, PAF causes gallbladder contraction through specific PAF receptors on gallbladder muscle. These PAF receptors appear to be linked to a prostaglandin-mediated mechanism and to pertussis toxin-sensitive G proteins. The contractile response is largely mediated through the utilization of extracellular calcium influx through voltage-dependent calcium channels.
Parkman
H P
HP
Departments of Medicine and Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. hparkman@nimbus.temple.edu
James
A N
AN
Ryan
J P
JP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D016473:Gallbladder Emptying / Q000187:drug effects*; D046934:Ginkgolides; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004224:Diterpenes; D016166:Free Radical Scavengers; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D011453:Prostaglandins; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D012433:Ryanodine; C045856:ginkgolide B; D037342:Pertussis Toxin; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium