title: Phenotype of neurons in the nucleus of the solitary tract that express CCK-induced activation of the ERK signaling pathway.
abstract: 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.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Babic
authors.forename: R Leigh
authors.initials: RL
authors.lastname: Townsend
authors.forename: Laurel M
authors.initials: LM
authors.lastname: Patterson
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sutton
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zheng
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Berthoud
mesh_terms: D000818:Animals; D002070:Butadienes / Q000008:administration & dosage; D002395:Catecholamines / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009570:Nitriles / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage*; D010641:Phenotype; D010766:Phosphorylation; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000235:genetics; D012527:Satiation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D012844:Sincalide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002070:Butadienes; D002395:Catecholamines; D020738:Leptin; D009570:Nitriles; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D054411:Receptors, Leptin; C113580:U 0126; C439758:cholecystokinin (26-33) sulfated amide; C515447:leptin receptor, mouse; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D012844:Sincalide