Mechanisms of proton-induced stimulation of CGRP release from rat antrum.
Mechanisms of acid-evoked CGRP release from gastric afferent nerves were investigated in rat antral mucosal/submucosal tissues. Low pH (pH 4.0, 5.0 and 6.0) stimulated antral CGRP release significantly and dose-dependently from rat antral fragments. Removal of extracellular calcium from the incubation medium resulted in significant inhibition (59%, P < 0.001) of acid (pH 4.0)-stimulated CGRP release. Conotoxin (1 x 10(-7) M), the selective blocker of N-type calcium channels, also significantly inhibited proton (pH 4.0)-induced CGRP release to values that were 74% below net stimulated levels. Neither nifedipine (1 x 10(-6) M), the L-type Ca(2+)-channel antagonist, nor indomethacin (1 x 10(-5) M), inhibitor of prostaglandin synthesis, altered acid-induced CGRP release. In contrast, ruthenium red (1 x 10(-5) M), capsaicin antagonist, almost completely prevented acid (pH 4.0)-stimulated CGRP release. Capsazepine (1 x 10(-4) M), a specific capsaicin receptor antagonist, also completely abolished acid-induced CGRP release. In conclusion, the results of these studies indicate that hydrogen ions are capable of evoking CGRP release from peripheral sensory neurons in rat antral mucosal/submucosal tissues. Proton-evoked CGRP release requires extracellular calcium and involves N-type calcium channels. Furthermore, acid appears to exert a capsaicin-like effect to evoke sensory neuropeptide release that is sensitive to capsazepine and ruthenium red. These data suggest that proton-induced antral CGRP release represents a direct action of hydrogen ions on mucosal/submucosal sensory dendritic nerve endings to effect local release of neuropeptide.
Ren
J
J
Division of Gastroenterology, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Wang
Y
Y
Liang
K
K
Gao
J
J
Brewer
K
K
Harty
R F
RF
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D013779:Tetrodotoxin; D002772:Cholera Toxin; D009543:Nifedipine; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin