Ketotifen prevents gastric hyperemia induced by intracisternal thyrotropin-releasing hormone at a low dose.
The thyrotropin-releasing hormone (TRH) analog, RX 77368, (p-Glu-His-(3,3'-dimethyl)-Pro-NH2) injected intracisternally (i.c.) at low doses increases gastric mucosal blood flow through vagal cholinergic and calcitonin gene-related peptide dependent pathways. The influence of the mast cell stabilizer, ketotifen, on i.c. injection of RX 77368 (1.5 ng)-induced changes in gastric mucosal blood flow (hydrogen gas-clearance technique), gastric acid secretion and mean arterial pressure was studied in urethane-anesthetized rats. RX 77368 increased gastric blood flow by 131% and systemic arterial pressure by 11 mm Hg and decreased gastric mucosal vascular resistance by 54% whereas acid secretion was not altered within the 30 min period post injection. Ketotifen had no effect on these basal parameters but abolished i.c. RX 77368-induced increased gastric mucosal blood flow and decreased gastric vascular resistance. These data suggest that mast cells may be part of the peripheral mechanisms involved in vagal gastric hyperemia induced by TRH analog injected i.c. at a low dose.
Király
A
A
CURE / Digestive Disease Research Center, West Los Angeles VA Medical Center, CA 90073, USA.
Süto
G
G
Guth
P H
PH
Taché
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002946:Cisterna Magna; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D006940:Hyperemia / Q000139:chemically induced / Q000517:prevention & control*; D007267:Injections; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D014655:Vascular Resistance / Q000187:drug effects
D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D011761:Pyrrolidonecarboxylic Acid; D007665:Ketotifen