BACKGROUND & AIMS: Sensory neurons play a critical role in reducing stress-induced gastric mucosal injury by releasing calcitonin gene-related peptide (CGRP) through an increase in gastric mucosal levels of prostacyclin (PGI(2)). Because estrogen enhances nerve growth factor-mediated CGRP production in sensory neurons, we hypothesized that stress-induced gastric mucosal injury occurs less in females than in males. METHODS: Gastric ulcer index, gastric myeloperoxidase activity, and gastric tissue levels of CGRP and 6-keto-PGF(1alpha), a stable metabolite of PGI(2), were determined in male and female wild-type (CGRP(+/+)) mice and CGRP knockout (CGRP(-/-)) mice subjected to water-immersion restraint stress. RESULTS: In CGRP(+/+) mice, ulcer index and myeloperoxidase activities were lower and gastric tissue levels of CGRP and 6-keto-PGF(1alpha) were higher in female mice than in male mice, but there were no such sex differences in CGRP(-/-)mice. Sex differences in CGRP(+/+) mice were eliminated by pretreatment with SB366791 (500 microg/kg intraperitoneally), a vanilloid receptor antagonist, and by ovariectomy. Reversal of sex differences by ovariectomy was not observed in female CGRP(+/+) mice with estradiol replacement (1 mg . kg(-1). wk(-1) for 3 weeks). Levels of CGRP messenger RNA in dorsal root ganglion neurons isolated from female CGRP(+/+) mice were decreased by ovariectomy, and these decreases were reversed by estradiol replacement. CONCLUSIONS: Estrogen-mediated increases in CGRP levels in sensory neurons might contribute to reduce stress-induced gastric mucosal injury by attenuating inflammatory responses. This might at least partly explain the sex difference observed in the development of stress-induced gastric mucosal injury in mice.
BACKGROUND & AIMS: Sensory neurons play a critical role in reducing stress-induced gastric mucosal injury by releasing calcitonin gene-related peptide (CGRP) through an increase in gastric mucosal levels of prostacyclin (PGI(2)). Because estrogen enhances nerve growth factor-mediated CGRP production in sensory neurons, we hypothesized that stress-induced gastric mucosal injury occurs less in females than in males. METHODS: Gastric ulcer index, gastric myeloperoxidase activity, and gastric tissue levels of CGRP and 6-keto-PGF(1alpha), a stable metabolite of PGI(2), were determined in male and female wild-type (CGRP(+/+)) mice and CGRP knockout (CGRP(-/-)) mice subjected to water-immersion restraint stress. RESULTS: In CGRP(+/+) mice, ulcer index and myeloperoxidase activities were lower and gastric tissue levels of CGRP and 6-keto-PGF(1alpha) were higher in female mice than in male mice, but there were no such sex differences in CGRP(-/-)mice. Sex differences in CGRP(+/+) mice were eliminated by pretreatment with SB366791 (500 microg/kg intraperitoneally), a vanilloid receptor antagonist, and by ovariectomy. Reversal of sex differences by ovariectomy was not observed in female CGRP(+/+) mice with estradiol replacement (1 mg . kg(-1). wk(-1) for 3 weeks). Levels of CGRP messenger RNA in dorsal root ganglion neurons isolated from female CGRP(+/+) mice were decreased by ovariectomy, and these decreases were reversed by estradiol replacement. CONCLUSIONS: Estrogen-mediated increases in CGRP levels in sensory neurons might contribute to reduce stress-induced gastric mucosal injury by attenuating inflammatory responses. This might at least partly explain the sex difference observed in the development of stress-induced gastric mucosal injury in mice.
Authors: Lei Zhang; Ji T Gong; Hu Q Zhang; Quan H Song; Guang H Xu; Lei Cai; Xiao D Tang; Hai F Zhang; Fang-E Liu; Zhan S Jia; Hong W Zhang Journal: J Neurogastroenterol Motil Date: 2015-03-30 Impact factor: 4.924