Nesfatin‐1 does not influence intracellular concentrations in subfornical organ neurons

The subfornical organ (SFO), a sensory circumventricular organ with a wide variety of peptidergic receptors, is an important central nervous system structure involved in the control of blood pressure (BP), food and water intake and energy homeostasis. Nesfatin‐1 (Nes‐1), a recently discovered anorectic peptide derived from the nucleobindin2 (NUCB2) precursor, has been shown to increase BP, decrease food and water intake and modulate energy balance. Microarray data confirms the presence of NUCB2 in the SFO. Electrophysiology from our lab verifies Nes‐1 influences dissociated SFO neurons. In order to investigate whether Nes‐1 influenced SFO neurons by changes in intracellular calcium [Ca 2+ ] i real time calcium imaging was used on dissociated SFO neurons. Bath application of Nes‐1 (10 −8 M n=26, 10 −7 M n=15) had no effect on [Ca 2+ ] i in dissociated neurons. In light of Nes‐1 effects on BP and drinking we investigated whether Nes‐1 would influence angiotensin II (AII) induced increases in [Ca 2+ ] i . Bath application of AII (10 −8 M) increased [Ca 2+ ] i (0.671± to 1.288± n=43) in 77% of SFO neurons. Co‐application of Nes‐1 (10 −8 M) and AII (10 −8 M) had no effect on AII induced increases in [Ca 2+ ] i as 72% of SFO neurons still demonstrated increased [Ca 2+ ] i (0.6691± to 1.196± n=33). Thus Nes‐1 has no influence on [Ca 2+ ] i in the SFO nor does it prevent AII induced increase of [Ca 2+ ] i . Funding: CIHR, HSFO, and NIH.