Stimulation of duodenal HCO₃⁻ secretion by hydrogen sulphide in rats: relation to prostaglandins, nitric oxide and sensory neurones.
OBJECTIVE
We examined the effect of H₂S on duodenal HCO₃⁻ secretion in rats and investigated the mechanism involved in this response.


METHODS
Animals were fasted for 18 h and anaesthetized with urethane. A duodenal loop was perfused with saline, and HCO₃⁻ secretion was measured at pH 7.0 using a pH stat-method. The loop was perfused at a rate of 0.2 mL min⁻¹ with NaHS (H₂S donor: 0.1-1 mm) for 5 min or 10 mm HCl for 10 min. Indomethacin or l-NAME [nitric oxide (NO) synthase inhibitor) was given s.c. 30 min or 3 h, respectively, before NaHS or acidification, while glibenclamide (K(ATP) channel blocker) or propargylglycine (cystathionine-g-lyase inhibitor) was given i.p. 30 min before.


RESULTS
Mucosal perfusion with NaHS dose dependently increased the HCO₃⁻ secretion, and this effect was significantly attenuated by indomethacin and l-NAME as well as by sensory deafferentation, but not by glibenclamide. Mucosal prostaglandin E₂ (PGE₂) production and luminal release of NO were both increased by NaHS perfusion. Mucosal acidification stimulated HCO₃⁻ secretion concomitant with an increase in PGE₂ and NO production, and these responses were mitigated by propargylglycine. The duodenal damage induced by acid (100 mm HCl for 4 h) was aggravated by pre-treatment with propargylglycine.


CONCLUSIONS
These results suggest that H₂S increases HCO₃⁻ secretion in the rat duodenum, and that this action is partly mediated by PG and NO as well as by capsaicin-sensitive afferent neurones. It is assumed that endogenous H₂S is involved in the regulatory mechanism of acid-induced HCO₃⁻ secretion and mucosal protection in the duodenum.
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
F
F
Ise
H
H
Takasuka
S
S
Hayashi
K
K
Takahashi
M
M
Koyama
E
E
Aihara
K
K
Takeuchi
D000393:Air Pollutants / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology
D000393:Air Pollutants; D000480:Alkynes; D001639:Bicarbonates; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D011453:Prostaglandins; D018689:Sensory System Agents; D013440:Sulfides; D009569:Nitric Oxide; C009055:propargylglycine; D019001:Nitric Oxide Synthase; C025451:sodium bisulfide; D015232:Dinoprostone; D002211:Capsaicin; D005905:Glyburide; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; D006862:Hydrogen Sulfide