Central vagal activation increases mucus gel thickness and surface cell intracellular pH in rat stomach.
OBJECTIVE
Central vagal stimulation induced by the thyrotropin-releasing hormone analogue RX 77368 injected intracisternally in urethane-anesthetized rats is gastroprotective. In an in vivo system, the effects of central RX 77368 on discrete components of the rat gastric mucosal barrier were studied to determine if these effects were prostaglandin synthesis dependent.


METHODS
Using intravital microscopy, intracellular pH of gastric surface cells, mucus gel thickness, gastric mucosal blood flow, and acid output were measured simultaneously in vivo.


RESULTS
Intracisternal RX 77368 significantly increased acid output, gel thickness, and blood flow. Indomethacin enhanced the RX 77368-induced increase in acid output but had no effect on measures of gastric defense during mucosal superfusion with neutral solutions. During acid superfusion, RX 77368 delayed acidification and enhanced recovery of surface cell intracellular pH. These latter effects were reversed partially by indomethacin. Omeprazole abolished RX 77368-induced acid secretion but did not alter its effects on gastric defense mechanisms.


CONCLUSIONS
In response to central vagal stimulation with RX 77368, gastric defense mechanisms were enhanced through prostaglandin-dependent and -independent pathways, in contrast to the prostaglandin-independent effects of intravenous pentagastrin. RX 77368-induced enhancements of gastric defense mechanisms did not occur as a result of acid secretion.
Tanaka
S
S
West Los Angeles Veterans Administration Medical Center, CURE: Digestive Diseases Research Center, Department of Medicine, California, USA.
Taché
Y
Y
Kaneko
H
H
Guth
P H
PH
Kaunitz
J D
JD
D000818:Animals; D001921:Brain / Q000502:physiology*; D005740:Gases / Q000097:blood; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D005782:Gels; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007276:Injections, Intraventricular; D008297:Male; D009093:Mucus / Q000737:chemistry* / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
D005740:Gases; D005782:Gels; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D006859:Hydrogen; D011761:Pyrrolidonecarboxylic Acid