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Role for ovarian hormones in purinoceptor-dependent natriuresis
- Source :
- Biology of Sex Differences, Biology of Sex Differences, Vol 11, Iss 1, Pp 1-10 (2020)
- Publication Year :
- 2020
- Publisher :
- BioMed Central, 2020.
-
Abstract
- 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.
- Subjects :
- Epithelial sodium channel
Male
medicine.medical_specialty
Purinoceptors
Ovariectomy
Natriuresis
lcsh:Medicine
Suramin
lcsh:Physiology
Cell Line
Gender Studies
Rats, Sprague-Dawley
Receptors, Purinergic P2Y2
Endocrinology
Sex Factors
Internal medicine
medicine
Renal medulla
Animals
RNA, Messenger
Receptor
Epithelial Sodium Channels
Sodium excretion
Kidney Medulla
Phospholipase C
Dose-Response Relationship, Drug
Estradiol
lcsh:QP1-981
Chemistry
Receptors, Purinergic P2
Research
Purinergic receptor
Ovary
lcsh:R
Rats
medicine.anatomical_structure
Gene Expression Regulation
Type C Phospholipases
Ovariectomized rat
Female
Hormone
Subjects
Details
- Language :
- English
- ISSN :
- 20426410
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Biology of Sex Differences
- Accession number :
- edsair.doi.dedup.....fe864fe7005e69c87c7b1768f53f6c54