Adropin acts in the rat paraventricular nucleus to influence neuronal excitability

作者:Loewen Spencer P; Ferguson Alastair V*
来源:American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2017, 312(4): R511-R519.
DOI:10.1152/ajpregu.00517.2016

摘要

Adropin is a peptide hormone with cardiovascular and metabolic roles in the periphery, including effects on glucose and lipid homeostasis. Central administration of adropin has been shown to inhibit water intake in rats; however, the site at which central adropin acts has yet to be elucidated. The hypothalamic paraventricular nucleus (PVN), a critical autonomic control center, plays essential roles in the control of fluid balance, energy homeostasis, and cardiovascular regulation, and is, therefore, a potential target for centrally acting adropin. In the present study, we used whole cell patch-clamp techniques to examine the effects of adropin on the excitability of neurons within the PVN. All three neuronal subpopulations (magnocellular, preautonomic, and neuroendocrine) in the PVN were found to be responsive to bathapplication of 10 nM adropin, which elicited responses in 68% of cells tested (n = 57/84). The majority of cells (58%) depolarized (5.2 +/- 0.3 mV; n = 49) in response to adropin, whereas the remaining responsive cells (10%) hyperpolarized (- 3.4 +/- 0.5 mV; n = 8), effects that were shown to be concentration-dependent. Additionally, responses were maintained in the presence of 1 mu M TTX in 75% of cells tested (n = 9/12), and voltage-clamp analysis revealed that adropin had no effect on the amplitude or frequency of excitatory or inhibitory postsynaptic currents (EPSCs and IPSCs) in PVN neurons, suggesting the peptide exerts direct, postsynaptic actions on these neurons. Collectively, these findings suggest central adropin may exert its physiological effects through direct actions on neurons in the PVN.

  • 出版日期2017-4