No role for prostacyclin IP receptors in duodenal HCO3- secretion induced by mucosal acidification in mice--comparison with capsaicin-induced response.
OBJECTIVE
We investigated the role of prostacyclin (PGI2) IP receptors in the acid-induced secretion of HCO3- using IP receptor knockout [IP (-/-)] mice, in comparison with capsaicin-induced secretion.


METHODS
Male C57/BL6 mice, both wild-type [WT] and [IP (-/-)], fasted for 18 h were used. Under urethane anesthesia, a proximal duodenal loop was perfused with saline, and the secretion of HCO3- was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. The secretion was stimulated by exposure of the loop to 10 mM HCl, capsaicin, PGE2 or cicaprost (a PGI2 agonist) for 10 min.


RESULTS
PGE2 stimulated HCO3- secretion in both WT and IP (-/-) mice, while cicaprost increased it in WT but not IP (-/-) mice. Luminal acidification increased the mucosal level of PGE2 as well as 6-keto-PGF1alpha, yet stimulated HCO3- secretion in both WT and IP (-/-) mice, in an indomethacin-inhibitable and sensory neuron-dependent manners. Perfusion of the duodenum with 20 mM HCl for 4 h caused severe damage in WT mice pretreated with indomethacin, but not in control WT or IP (-/-) mice. Capsaicin increased duodenal HCO3- secretion in WT mice, in an indomethacin-sensitive manner, yet no such response was observed in the animals lacking IP receptors.


CONCLUSIONS
The presence of IP receptors is not essential for acid-induced HCO3- secretion and mucosal defense against acid injury in the duodenum, although activation of IP receptors results in stimulation of HCO3- secretion. Although duodenal HCO3- secretion induced by both acid and capsaicin depends on afferent neurons, it seems that the mode of interaction with the afferent neurons differs regarding dependency on the PGI2/IP receptors.
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
Masato
M
Nakashima
Masako
M
Aoi
Eitaro
E
Aihara
Koji
K
Takeuchi
D000818:Animals; D001639:Bicarbonates / Q000032:analysis*; D002211:Capsaicin / Q000494:pharmacology*; D004386:Duodenum / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044006:Receptors, Epoprostenol / Q000502:physiology*
D001639:Bicarbonates; D044006:Receptors, Epoprostenol; D002211:Capsaicin