Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-56278
Potes, C S; Boyle, C N; Wookey, P J; Riediger, T; Lutz, T A (2012). Involvement of the extracellular-signal regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 302(3):R340-51.
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Peripheral amylin inhibits eating via the area postrema (AP). Because amylin activates the extracellular-signal regulated kinase 1/2 (ERK) pathway in some tissues, and because ERK1/2 phosphorylation (pERK) leads to acute neuronal responses, we postulated that it may be involved in amylin's eating inhibitory effect. Amylin-induced ERK phosphorylation (pERK) was investigated by immunohistochemistry in brain sections containing the AP. pERK-positive AP-neurons were double-stained for the calcitonin 1a/b receptor, which is part of the functional amylin-receptor. AP sections were also phenotyped using dopamine-beta-hydroxylase (DBH) as a marker of noradrenergic neurons. The effect of fourth ventricular administration of the ERK cascade blocker U0126 on amylin's eating inhibitory action was tested in feeding trials. The number of pERK-positive neurons in the AP was highest approximately 10-15 min after amylin treatment; the effect appeared to be dose-dependent (5-20 μg/kg amylin). A portion of pERK-positive neurons in the AP carried the amylin-receptor and 22% of the pERK-positive neurons were noradrenergic. Pre-treatment of rats with U0126 decreased the number of pERK-positive neurons in the AP after amylin injection. U0126 also attenuated the ability of amylin to reduce eating, at least when the animals had been fasted 24h prior to the feeding trial. Overall, our results suggest that amylin directly stimulates pERK in AP neurons in a time- and dose-dependent manner. Part of the AP neurons displaying pERK were noradrenergic. At least under fasting conditions, pERK was shown to be a necessary part in the signaling cascade mediating amylin's anorectic effect.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology|
05 Vetsuisse Faculty > Institute of Veterinary Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||28 Jan 2012 20:44|
|Last Modified:||09 Jan 2013 05:28|
|Publisher:||American Physiological Society|
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