Stimulation by bradykinin of HCO3- secretion in rat gastroduodenal mucosa.
BACKGROUND
We examined the effect of bradykinin on gastroduodenal HCO(3)(-) secretion in rats and investigated the mechanisms involved in this action.


METHODS
Under urethane anesthesia, a chambered stomach or a proximal duodenal loop was perfused with saline, and the secretion of HCO(3)(-) was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl.


RESULTS
Intravenous administration of bradykinin increased both gastric and duodenal HCO(3)(-) secretion in a dose-dependent manner. These effects were totally blocked by FR172357, the bradykinin B2 receptor antagonist, and significantly attenuated by indomethacin or L-NAME, although the degree of inhibition was much greater in the stomach than the duodenum. Likewise, the response to bradykinin in the stomach totally disappeared on the chemical ablation of capsaicin-sensitive afferent neurons, whereas this action in the duodenum was inhibited only partially by sensory deafferentation. Capsazepine, the antagonist of transient receptor potential vanilloid type 1 (TRPV1), did not significantly affect the HCO(3)(-) response to bradykinin in these tissues.


CONCLUSIONS
Bradykinin increases both gastric and duodenal HCO(3)(-) secretion through the activation of B2 receptors, and this action is mediated locally by endogenous prostaglandins (PGs) and nitric oxide (NO) as well as capsaicin-sensitive afferent neurons. It is assumed that bradykinin causes the release of PGs and NO as well as activation of afferent neurons via B2 receptors but not through the interaction with TRPV1, and these factors are all involved in the gastroduodenal responses, although the mode of interaction between these factors may be different in the stomach and duodenum.
Aihara
Eitaro
E
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Hayashi
Masamune
M
Nomura
Yoko
Y
Kato
Shinichi
S
Takeuchi
Koji
K
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004386:Duodenum / Q000033:anatomy & histology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D065094:Bradykinin B2 Receptor Antagonists; D004791:Enzyme Inhibitors; C106745:FR 167344; D011725:Pyridines; C071423:capsazepine; D002211:Capsaicin; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin