CALL FOR PAPERS Neural Integration of Peripheral Signals Implicated in the Control of Energy Homeostasis and Metabolism Phenotype of neurons in the nucleus of the solitary tract that express CCK-induced activation of the ERK signaling pathway

Babic T, Townsend RL, Patterson LM, Sutton GM, Zheng H, Berthoud HR. Phenotype of neurons in the nucleus of the solitary tract that express CCK-induced activation of the ERK signaling pathway. Am J Physiol Regul Integr Comp Physiol 296: R845–R854, 2009. First published January 28, 2009; doi:10.1152/ajpregu.90531.2008.—The satiating potency of CCK has been well characterized, including its mediation by capsaicin-sensitive vagal primary afferents. We have previously shown that peripherally administered CCK activates the MAPK-signaling cascade in a population of nucleus of the solitary tract (NTS) neurons and that preventing ERK1/2 phosphorylation partly attenuates CCK’s satiating potency. The aim of this study was to identify the neurochemical phenotypes of the NTS neurons that exhibit CCK-induced activation of ERK1/2. Using confocal microscopy, we demonstrate that intraperitoneal CCK administration increases the number of neurons that express phosphorylated ERK1/2 (pERK1/2) in the medial and commissural subnuclei of the NTS and that CCK-induced expression of ERK1/2 is increased in tyrosine hydroxylase-immunoreactive neurons. Using Western blot analysis, we show that the robust increase in tyrosine hydroxylase phosphorylation obtained with intraperitoneal CCK is significantly attenuated in rats pretreated with the ERK-pathway blocker U0126 injected into the 4th ventricle. In addition, CCK injections increased pERK1/2 expression in POMC neurons in the NTS. In contrast, only the rare GAD67, neuronal nitric oxide synthase, and leptin-responsive neuron exhibited CCK-induced pERK immunoreactivity. We conclude that activation of POMC-immunoreactive neurons and tyrosine hydroxylase activity via the ERK-signaling pathway in the NTS likely contributes to CCK’s satiating effects.