help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on June 16, 2005
Endocrinology, doi:10.1210/en.2005-0562
A more recent version of this article appeared on September 1, 2005
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
146/9/3739    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sutton, G. M.
Right arrow Articles by Berthoud, H.-R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sutton, G. M.
Right arrow Articles by Berthoud, H.-R.

Submitted on May 10, 2005
Accepted on June 8, 2005

Melanocortinergic modulation of cholecystokinin-induced suppression of feeding through ERK signaling in rat solitary nucleus

Gregory M. Sutton, Bronwyn Duos, Laurel M. Patterson, and Hans-Rudolf Berthoud*

Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA

* To whom correspondence should be addressed. E-mail: berthohr{at}pbrc.edu.

Signals from the gut and hypothalamus converge in the caudal brain stem to control ingestive behavior. We have previously shown that phosphorylation of the extracellular-signal regulated kinase (ERK1/2) in the solitary nucleus (NTS) is necessary for food intake suppression by exogenous CCK. Here, we test whether this intracellular signaling cascade is also involved in the integration of melanocortin-receptor mediated inputs to the caudal brain stem. Using 4th ventricular-cannulated rats and Western blotting of NTS tissue, we show that the MC4R agonist MTII rapidly and dose-dependently increases phosphorylation of both ERK1/2 and CREB. Sequential administration of 4th ventricular MTII and peripheral CCK at doses that alone produced submaximal stimulation of pERK1/2 produced an additive increase. Prior 4th ventricular administration of the MC4R antagonist SHU9119 completely abolished the CCK-induced increases in pERK and pCREB and in freely feeding rats, SHU9119 significantly increased meal size and satiety ratio. Prior administration of the MEK-inhibitor U0126 abolished the capacity of MTII to suppress 2-h food intake and significantly decreased MTII-induced ERK phosphorylation in the NTS. Furthermore, pretreatment with the cAMP inhibitor, cAMPS-Rp, significantly attenuated stimulation of pERK induced by either CCK or MTII. The results demonstrate that activation of the ERK pathway is necessary for peripheral CCK and central MTII to suppress food intake. The cAMP->ERK->CREB cascade may thus constitute a molecular integrator for converging satiety signals from the gut and adiposity signals from the hypothalamus in the control of meal size and food intake.
Key words: MC4R • satiation • satiety • brainstem • CREB • cAMP




This article has been cited by other articles:


Home page
 J. Neurosci.Home page
S. Wan, K. N. Browning, F. H. Coleman, G. Sutton, H. Zheng, A. Butler, H.-R. Berthoud, and R. A. Travagli
Presynaptic Melanocortin-4 Receptors on Vagal Afferent Fibers Modulate the Excitability of Rat Nucleus Tractus Solitarius Neurons
J. Neurosci., May 7, 2008; 28(19): 4957 - 4966.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. A. Czyzyk, M. A. Sikorski, L. Yang, and G. S. McKnight
Disruption of the RII subunit of PKA reverses the obesity syndrome of agouti lethal yellow mice
PNAS, January 8, 2008; 105(1): 276 - 281.
[Abstract] [Full Text] [PDF]

Home page
 J ANIM SCIHome page
J. C. MacDonald, T. J. Klopfenstein, G. E. Erickson, and W. A. Griffin
Effects of dried distillers grains and equivalent undegradable intake protein or ether extract on performance and forage intake of heifers grazing smooth bromegrass pastures
J Anim Sci, October 1, 2007; 85(10): 2614 - 2624.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
H. D. Sun, M. Malabunga, J. R. Tonra, R. DiRenzo, F. E. Carrick, H. Zheng, H.-R. Berthoud, O. P. McGuinness, J. Shen, P. Bohlen, et al.
Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys
Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E964 - E976.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. A. Sebag and P. M. Hinkle
Regulation of Endogenous Melanocortin-4 Receptor Expression and Signaling by Glucocorticoids
Endocrinology, December 1, 2006; 147(12): 5948 - 5955.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. G. Baskin
Single-minded view of melanocortin signaling in energy homeostasis.
Endocrinology, October 1, 2006; 147(10): 4539 - 4541.
[Full Text] [PDF]

Home page
 EndocrinologyHome page
K. L. J. Ellacott, I. G. Halatchev, and R. D. Cone
Characterization of Leptin-Responsive Neurons in the Caudal Brainstem
Endocrinology, July 1, 2006; 147(7): 3190 - 3195.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2005 by The Endocrine Society