Platelet-activating factor stimulates gastric acid secretion in isolated rabbit gastric glands.
We examined the effect of platelet-activating factor (PAF) on gastric acid secretion by isolated rabbit gastric glands as determined by [14C]aminopyrine ([14C]AP) uptake. PAF, histamine, and carbachol time- and concentration-dependently stimulated [14C]AP uptake, with estimated half-maximal effective concentrations of 60 pM, 0.25 microM, and 0.1 microM, respectively. PAF-induced [14C]AP uptake was inhibited by the specific PAF antagonists BN-50727 and SR-27417 and by the proton pump inhibitors omeprazole and lansoprazole. However, the H2-receptor antagonist famotidine had no effect. Buffering extracellular Ca2+ by ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid resulted in a shift to the right of the time-course effect of PAF without altering the maximal response, whereas buffering intracellular Ca2+ by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid 2-acetoxymethyl ester, as well as blocking Ca2+ channels by verapamil, inhibited PAF-induced [14C]AP uptake. Intracellular Ca2+ concentration in isolated rabbit gastric glands, as measured by fura 2-acetoxymethyl ester, concentration-dependently increased in response to PAF, to a maximum of 1.5-fold for 0.1 microM. These results suggest that PAF stimulates gastric acid secretion via specific receptors activating intracellular Ca2+ mobilization, which could be located on the parietal cells.
Sobhani
I
I
Unité de Recherche de Gastroentérologie, Institut National de la Santé et de la Recherche Médicale Unité 10, Hôpital Bichat, Paris. France.
Bado
A
A
Moizo
L
L
Laigneau
J P
JP
Tarrade
T
T
Braquet
P
P
Lewin
M J
MJ
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D005456:Fluorescent Dyes; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D001381:Azepines; D005456:Fluorescent Dyes; D010972:Platelet Activating Factor; D013844:Thiazoles; D058924:Thienopyridines; D014230:Triazoles; D000632:Aminopyrine; D004533:Egtazic Acid; D015738:Famotidine; D006632:Histamine; D002217:Carbachol; D014700:Verapamil; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; C067429:Setipafant; C071317:Foropafant