Affiliation:
1. Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Abstract
Although the morbidity of ulcers is statistically higher in males than females, the mechanism of this
difference remains unknown. Recent studies show that duodenal HCO3
- response to mucosal acidification is
higher in females than males, and this may be a factor responsible for the sex difference in the mucosal protective
mechanisms. In this article, we examined the duodenal HCO3
- responses to various stimuli in male and female
rats, including estrogen, and reviewed the mechanisms responsible for the sex difference in the acid-induced
HCO3
- secretion. Mucosal acidification was performed by exposing the duodenum to 10 mM HCl for 10 min.
PGE2 was administered intravenously, while capsaicin was applied topically to the duodenum for 10 min. Tamoxifen
was given s.c. 30 min before the acidification. Ovariectomy was performed 2 weeks before the experiments;
half of the animals were given estrogen i.m. after the operation. Mucosal acidification increased duodenal
HCO3
- secretion in male rats, and this response was inhibited by indomethacin and sensory deafferentation. Although
no sex difference was found in HCO3
- responses to PGE2 and capsaicin, the response to acid was significantly
greater in female than male rats. The different HCO3
- response to acid disappeared on ovariectomy, and
this effect was totally reversed by the repeated administration of estrogen. The gene expression of ASIC3 in female
rats was greater than in male rats and down-regulated by ovariectomy or tamoxifen treatment in an estradiol-
dependent manner, while no sex difference was observed in TRPV1 and CFTR expressions. In conclusion,
the acid-induced HCO3
- response is greater in female than male rats, and this phenomenon is not due to changes
in PGE2 sensitivity or TRPV1/CFTR expressions but may be accounted for by increased expression of ASIC3 on
sensory neurons, which is associated with the chronic influence of estrogen.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
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