Abstract
A novel regulator of thirst behavior: phoenixin. Am J Physiol Regul Integr Comp Physiol 318: R1027-R1035, 2020. First published April 15, 2020; doi:10.1152/ajpregu.00023.2020.-There are examples of physiological conditions under which thirst is inappropriately exaggerated, and the mechanisms for these paradoxical ingestive behaviors remain unknown. We are interested in thirst mechanisms across the female life cycle and have identified a novel mechanism through which ingestive behavior may be activated. We discovered a previously unrecognized endogenous hypothalamic peptide, phoenixin (PNX), identified physiologically relevant actions of the peptide in brain and pituitary gland to control reproductive hormone secretion in female rodents, and in the process identified the previously orphaned G protein-coupled receptor Gpr173 to be a potential receptor for the peptide. Labeled PNX binding distribution in brain parallels areas known to be important in ingestive behaviors as well in areas where gonadal steroids feedback to control estrous cyclicity (Stein LM, Tullock CW, Mathews SK, Garcia-Galiano D, Elias CF, Samson WK, Yosten GLC, Am J Physiol Regul Integr Comp Physiol 311: R489-R496, 2016). We have demonstrated upregulation of Gpr173 during puberty, fluctuations across the estrous cycle, and, importantly, upregulation during the last third of gestation. It is during this hypervolemic, hyponatremic state that both vasopressin secretion and thirst are inappropriately elevated in humans. Here, we show that central administration of PNX stimulated water drinking in both males and females under ad libitum conditions, increased water drinking after overnight fluid deprivation, and increased both water and 1.5% NaCl ingestion under fed and hydrated conditions. Importantly, losartan pretreatment blocked the effect of PNX on water drinking, and knockdown of Gpr173 by use of short interfering RNA constructs significantly attenuated water drinking in response to overnight fluid deprivation. These actions, together with the stimulatory action of PNX on vasopressin secretion, suggest that this recently discovered neuropeptide may impact the recruitment of critically important neural circuits through which ingestive behaviors and endocrine mechanisms that maintain fluid and electrolyte homeostasis are regulated.
Recommended Citation
C. J. Haddock et al., "A Novel Regulator of Thirst Behavior: Phoenixin," American Journal of Physiology Regulatory Integrative and Comparative Physiology, vol. 318, no. 6, pp. R1027 - R1035, American Physiological Society, May 2020.
The definitive version is available at https://doi.org/10.1152/ajpregu.00023.2020
Department(s)
Biological Sciences
Publication Status
Open Access
Keywords and Phrases
angiotensin II; fluid and electrolyte homeostasis; phoenixin; salt appetite; thirst
International Standard Serial Number (ISSN)
1522-1490; 0363-6119
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 American Physiological Society, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
20 May 2020
PubMed ID
32292064
Comments
National Institutes of Health, Grant HL-121456