Phenotype of neurons in the nucleus of the solitary tract that express CCK-induced activation of the ERK signaling pathway

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 296; no. 4; p. R845
• Main Authors: Babic, Tanja, Townsend, R Leigh, Patterson, Laurel M, Sutton, Gregory M, Zheng, Huiyuan, Berthoud, Hans-Rudolf
• Format: Journal Article
• Language: English
• Published: United States 01-04-2009
• Subjects: Animals; Butadienes - administration & dosage; Catecholamines - metabolism; Enzyme Activation; Female; Glutamate Decarboxylase - genetics; Green Fluorescent Proteins - genetics; Injections, Intraperitoneal; Injections, Intraventricular; Leptin - metabolism; Male; Mice; Mice, Transgenic; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; Neurons - drug effects; Neurons - enzymology; Nitric Oxide Synthase Type I - metabolism; Nitriles - administration & dosage; Peptide Fragments - administration & dosage; Phenotype; Phosphorylation; Pro-Opiomelanocortin - genetics; Promoter Regions, Genetic; Protein Kinase Inhibitors - administration & dosage; Rats; Rats, Sprague-Dawley; Receptors, Leptin - genetics; Satiation - drug effects; Signal Transduction - drug effects; Sincalide - administration & dosage; Sincalide - analogs & derivatives; Solitary Nucleus - cytology; Solitary Nucleus - drug effects; Solitary Nucleus - enzymology; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0363-6119
• 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.