Genetic interaction of purinergic P2X7 receptor and ER-α polymorphisms in susceptibility to osteoporosis in Chinese postmenopausal women

Wang, Hui; Gong, Chang; Liu, Xingzi; Rao, Shenqiang; Li, Tao; He, Luling; Nie, Yijun; Wang, Shuo; Zhong, Peipei; Xue, Yansong; Wang, Jihong; Zhao, Junsan; Zhou, Yuru; Ding, Lu; Tu, Yunming; Yang, Yuping; Xiong, Chaopeng; Liang, Shangdong; Xu, Hong

doi:10.1007/s00774-017-0862-3

Cited by 18 publications

(7 citation statements)

References 43 publications

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“…This observation directed us to focus on the P2Y2/P2Y4 signaling cascade as a potential contributor to sex-related physiological differences in renal salt handling. This is particularly relevant to evidence demonstrating that sex hormones regulate extrarenal purinoceptor signaling [31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Role for ovarian hormones in purinoceptor-dependent natriuresis

Gohar

Kasztan

Zhang

et al. 2020

Preprint

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Background: Premenopausal women have a lower risk of hypertension compared to age-matched men and postmenopausal women. P2Y 2 and P2Y 4 purinoceptor can be considered potential contributors to hypertension due to their emerging roles in regulating renal tubular Na + transport. Activation of these receptors inhibits epithelial Na + channel activity (ENaC) via a phospholipase C (PLC)-dependent pathway resulting in natriuresis. We recently reported that activation of P2Y 2 and P2Y 4 receptors in the renal medulla by UTP promotes natriuresis in male and ovariectomized (OVX) rats, but not in ovary-intact females. This led us to hypothesize that ovary-intact females have greater basal renal medullary activity of P2 (P2Y 2 and P2Y 4 ) receptors regulating Na + excretion compared to male and OVX rats. Methods: To test our hypothesis, we determined (i) the effect of inhibiting medullary P2 receptors by suramin (750 μg/kg/min) on urinary Na + excretion in anesthetized male, ovary-intact female and OVX Sprague Dawley rats, (ii) mRNA expression and protein abundance of P2Y 2 and P2Y 4 receptors and (iii) mRNA expression of their downstream effectors (PLC-1d and ENaCa) in renal inner medullary tissues obtained from these three groups. We also subjectedcultured mouse inner medullary collecting duct cells (segment 3, mIMCD3) to different concentrations of 17ß-estradiol(E 2 , 0, 10, 100 and 1000 nM) to test whether E 2 increases mRNA expression of P2Y 2 and P2Y 4 receptors. Results: Acute P2 inhibition attenuated urinary Na + excretion in ovary-intact females, but not in male or OVX rats.We found that P2Y 2 and P2Y 4 mRNA expression was higher in the inner medulla from females compared to males or OVX. Inner medullary lysates showed that ovary-intact females have higher P2Y 2 receptor protein abundance, compared to males, however, OVX did not eliminate this sex difference. We also found that E 2 dose-dependently upregulated P2Y 2 and P2Y 4 mRNA expression in mIMCD3. Conclusion: These data suggest that females have enhanced P2Y 2 and P2Y 4 -dependent regulation of Na + handling in the renal medulla, compared to male and OVX rats. We speculate that the P2 pathway contributes to facilitated renal Na + handling in premenopausal females.

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Section: Discussionmentioning

confidence: 99%

Role for ovarian hormones in purinoceptor-dependent natriuresis

Gohar

Kasztan

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This observation directed us to focus on the P2Y 2 /P2Y 4 signaling cascade as a potential contributor to sexrelated physiological differences in renal salt handling. This is particularly relevant to evidence demonstrating that sex hormones regulate extrarenal purinoceptor signaling [35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Role for ovarian hormones in purinoceptor-dependent natriuresis

Gohar

Kasztan

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Premenopausal women have a lower risk of hypertension compared to age-matched men and postmenopausal women. P2Y2 and P2Y4 purinoceptor can be considered potential contributors to hypertension due to their emerging roles in regulating renal tubular Na+ transport. Activation of these receptors inhibits epithelial Na+ channel activity (ENaC) via a phospholipase C (PLC)-dependent pathway resulting in natriuresis. We recently reported that activation of P2Y2 and P2Y4 receptors in the renal medulla by UTP promotes natriuresis in male and ovariectomized (OVX) rats, but not in ovary-intact females. This led us to hypothesize that ovary-intact females have greater basal renal medullary activity of P2 (P2Y2 and P2Y4) receptors regulating Na+ excretion compared to male and OVX rats. Methods: To test our hypothesis, we determined (i) the effect of inhibiting medullary P2 receptors by suramin (750 μg/kg/min) on urinary Na+ excretion in anesthetized male, ovary-intact female and OVX Sprague Dawley rats, (ii) mRNA expression and protein abundance of P2Y2 and P2Y4 receptors and (iii) mRNA expression of their downstream effectors (PLC-1d and ENaCa) in renal inner medullary tissues obtained from these three groups. We also subjected cultured mouse inner medullary collecting duct cells (segment 3, mIMCD3) to different concentrations of 17ß-estradiol (E2, 0, 10, 100 and 1000 nM) to test whether E2 increases mRNA expression of P2Y2 and P2Y4 receptors.Results: Acute P2 inhibition attenuated urinary Na+ excretion in ovary-intact females, but not in male or OVX rats. We found that P2Y2 and P2Y4 mRNA expression was higher in the inner medulla from females compared to males or OVX. Inner medullary lysates showed that ovary-intact females have higher P2Y2 receptor protein abundance, compared to males, however, OVX did not eliminate this sex difference. We also found that E2 dose-dependently upregulated P2Y2 and P2Y4 mRNA expression in mIMCD3. Conclusion: These data suggest that ovary-intact females have enhanced P2Y2 and P2Y4-dependent regulation of Na+ handling in the renal medulla, compared to male and OVX rats. We speculate that the P2 pathway contributes to facilitated renal Na+ handling in premenopausal females.

show abstract

“…This observation directed us to focus on the P2Y 2 /P2Y 4 signaling cascade as a potential contributor to sex-related physiological differences in renal salt handling. This is particularly relevant to evidence demonstrating that sex hormones regulate extrarenal purinoceptor signaling [35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Role for ovarian hormones in purinoceptor-dependent natriuresis

et al. 2020

View full text Add to dashboard Cite

Background Premenopausal women have a lower risk of hypertension compared to age-matched men and postmenopausal women. P2Y2 and P2Y4 purinoceptor can be considered potential contributors to hypertension due to their emerging roles in regulating renal tubular Na+ transport. Activation of these receptors inhibits epithelial Na+ channel activity (ENaC) via a phospholipase C (PLC)-dependent pathway resulting in natriuresis. We recently reported that activation of P2Y2 and P2Y4 receptors in the renal medulla by UTP promotes natriuresis in male and ovariectomized (OVX) rats, but not in ovary-intact females. This led us to hypothesize that ovary-intact females have greater basal renal medullary activity of P2 (P2Y2 and P2Y4) receptors regulating Na+ excretion compared to male and OVX rats. Methods To test our hypothesis, we determined (i) the effect of inhibiting medullary P2 receptors by suramin (750 μg/kg/min) on urinary Na+ excretion in anesthetized male, ovary-intact female, and OVX Sprague Dawley rats, (ii) mRNA expression and protein abundance of P2Y2 and P2Y4 receptors, and (iii) mRNA expression of their downstream effectors (PLC-1δ and ENaCα) in renal inner medullary tissues obtained from these three groups. We also subjected cultured mouse inner medullary collecting duct cells (segment 3, mIMCD3) to different concentrations of 17ß-estradiol (E2, 0, 10, 100, and 1000 nM) to test whether E2 increases mRNA expression of P2Y2 and P2Y4 receptors. Results Acute P2 inhibition attenuated urinary Na+ excretion in ovary-intact females, but not in male or OVX rats. We found that P2Y2 and P2Y4 mRNA expression was higher in the inner medulla from females compared to males or OVX. Inner medullary lysates showed that ovary-intact females have higher P2Y2 receptor protein abundance, compared to males; however, OVX did not eliminate this sex difference. We also found that E2 dose-dependently upregulated P2Y2 and P2Y4 mRNA expression in mIMCD3. Conclusion These data suggest that ovary-intact females have enhanced P2Y2 and P2Y4-dependent regulation of Na+ handling in the renal medulla, compared to male and OVX rats. We speculate that the P2 pathway contributes to facilitated renal Na+ handling in premenopausal females.

show abstract

Genetic interaction of purinergic P2X7 receptor and ER-α polymorphisms in susceptibility to osteoporosis in Chinese postmenopausal women

Cited by 18 publications

References 43 publications

Role for ovarian hormones in purinoceptor-dependent natriuresis

Role for ovarian hormones in purinoceptor-dependent natriuresis

Role for ovarian hormones in purinoceptor-dependent natriuresis

Role for ovarian hormones in purinoceptor-dependent natriuresis

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