Mechanism of the contractile response to platelet-activating factor (PAF) of the rat stomach fundus. I. PAF-induced contractile response and calcium mobilization.
1. Platelet-activating factor (PAF) caused contraction of the rat stomach fundus in a concentration-dependent manner in the presence of atropine, guanethidine, chlorpheniramine, methylsergide, indomethacin, nordihydroguaiaretic acid and tetrodotoxin. 2. PAF produced phasic contraction followed by tonic contraction. The PAF-induced tonic contraction was significantly reduced by treatment with CV-6209, an antagonist of PAF, but phasic contraction induced by PAF was rather resistant to CV-6209. 3. The contraction induced by PAF was markedly reduced when tissues were previously exposed to PAF (desensitization). 4. Nicardipine reduced the PAF-induced phasic contraction but not of the tonic contraction. 5. PAF-induced contractions were almost abolished in Ca(2+)-free medium. 6. The Ca(2+)-contraction in Ca(2+)-free solution was significantly augmented by PAF, whereas the Ca(2+)-contraction in Ca(2+)-free, isotonic high K+ (60 mM) medium was unaffected by PAF. 7. These results suggest that PAF-induced contractile response in the rat stomach fundus is due to an influx of Ca2+ through voltage-dependent Ca(2+)-channels (VDC) and receptor-operated Ca(2+)-channels (ROC). It is further suggested that PAF may depolarize the stomach fundus and this depolarization may open the VDC, whereas PAF may not act directly on the VDC.
Kamata
K
K
Department of Pharmacology, School of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Arai
Y
Y
Kasuya
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005748:Gastric Fundus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; D009529:Nicardipine; D002118:Calcium