Study of platelet activating factor and its antagonists on rat colon strip with a new method avoiding tachyphylaxis.
Platelet activating factor induced slow, but sustained contraction of isolated rat colon in a dose-dependent manner. The contraction persisted even when the strips were washed several times with Tyrode solution. However, the addition of high concentrations of bovine serum albumin to the washing solution led to the rapid relaxation of the strips to the basal level, possibly by removing platelet activating factor tightly bound to rat colon. These strips then responded normally to a second addition of platelet activating factor. Neither the cholinergic nervous system nor release of histamine, serotonin, prostaglandins or leukotriene D4 were significantly involved in the contraction induced by platelet activating factor. FR-900452 and CV-3988, recently found to be antagonists of platelet activating factor, selectively blocked the contraction of rat colon induced by the active phospholipid, indicating that it induced contraction by a direct stimulatory effect on the smooth muscle of rat colon in a receptor-mediated manner.
Tokumura
A
A
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Terao
M
M
Okamoto
M
M
Yoshida
K
K
Tsukatani
H
H
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002744:Chlorpheniramine / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors; D012709:Serum Albumin / Q000494:pharmacology; D013618:Tachyphylaxis
D002867:Chromones; D010972:Platelet Activating Factor; D013189:SRS-A; D012709:Serum Albumin; D002744:Chlorpheniramine; D001285:Atropine; C006312:FPL 55712; D007213:Indomethacin; D008784:Methysergide