CNS effects of platelet-activating factor on the rat stomach.
PAF has been implicated in the pathogenesis of acute gastric injury. When administered peripherally, PAF induces severe gastric mucosal damage. PAF-metabolizing enzymes are present in the brain, but the central effects of PAF on the stomach are unknown. We have investigated gastric secretory and mucosal response to i.c.v. PAF in the rat and compared it with that of i.c.v. thyrotropin-releasing hormone (TRH), a known central gastric secretagogue. Gastric acid output was markedly increased by TRH (171.6 +/- 26.3 mumol/h mean +/- SE) and by 20 micrograms/kg/h i.v. pentagastrin (107.6 +/- 23.6), as compared to controls receiving i.c.v. vehicle (20.2 +/- 7.5; p less than 0.01 for both). In contrast, acid output decreased after i.c.v. PAF (13.5 +/- 7.5). Furthermore, i.c.v. PAF markedly inhibited acid output stimulated by i.v. pentagastrin (45.1 +/- 7.03; p less than 0.05). Morphologic studies showed acute gastric mucosal erosions after i.c.v. TRH, but no damage was observed after i.c.v. PAF or vehicle. Thus, i.c.v. PAF inhibits gastric acid secretion but does not alter gastric mucosal integrity, whereas i.c.v. TRH stimulates acid secretion and induces gastric injury. The opposite effects of PAF and TRH suggest the existence of a gastric modulatory system at the central level.
Cucala
M
M
Digestive System Research Unit, Vall d'Hebron General Hospital, Barcelona, Spain.
Wallace
J L
JL
Salas
A
A
Guarner
F
F
Rodríguez
R
R
Malagelada
J R
JR
D000818:Animals; D001921:Brain / Q000187:drug effects*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007276:Injections, Intraventricular; D010437:Peptic Ulcer / Q000139:chemically induced / Q000473:pathology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D013270:Stomach / Q000187:drug effects*
D010972:Platelet Activating Factor