Mechanisms mediating gastric hyperemic and acid responses to central TRH analog at a cytoprotective dose.
Gastric hyperemic and acid responses to the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a cytoprotective dose were investigated, as well as the underlying mechanisms of the responses. Gastric acid secretion (GAS), mucosal blood flow (GMBF; measured by the hydrogen gas clearance technique), and mucosal vascular resistance (GMVR) and mean arterial pressure (MAP) were assessed simultaneously for 30 min before and after RX-77368 (1.5 ng) administration in urethan-anesthetized rats. RX-77368 increased GMBF from 46.8 +/- 5.3 to 100.6 +/- 20.9 ml.min-1.100 g-1 and MAP from 70.3 +/- 2.1 to 84.3 +/- 5.9 mmHg and decreased GMVR from 1.50 +/- 0.33 to 0.84 +/- 0.08 mmHg.ml-1.min.100 g, whereas GAS was not significantly altered (1.8 +/- 0.4 vs. 4.7 +/- 1.7 mumol/30 min) in vehicle-pretreated rats. The GMBF, MAP, and GMVR responses to RX-77368 were not modified by indomethacin (5 mg/kg ip), whereas GAS was increased. In rats pretreated with capsaicin (125 mg/kg sc) or calcitonin gene-related peptide (CGRP) antagonist hCGRP-(8-37), intracisternal RX-77368 did not increase GMBF or decrease GMVR but did stimulate GAS. These data show that vagal stimulation by the TRH analog RX-77368 injected intracisternally at a nonacid secretory dose increases GMBF. Gastric hyperemia is mediated by CGRP contained in capsaicin-sensitive afferent fibers, whereas acid secretion is under the inhibitory influence of prostaglandins and CGRP.
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Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, California, USA.
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D000818:Animals; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects*; D006940:Hyperemia; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D011761:Pyrrolidonecarboxylic Acid; D007213:Indomethacin