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- Title
Melanocortin Signaling in the Brainstem Influences Vagal Outflow to the Stomach.
- Authors
Richardson, Janell; Cruz, Maureen T.; Majumdar, Usnish; Lewin, Amanda; Kingsbury, Kathryn A.; Dezfuli, Ghazaul; Vicini, Stefano; Verbalis, Joseph G.; Dretchen, Kenneth L.; Gillis, Richard A.; Sahibzada, Niaz
- Abstract
Activation of melanocortin 4 receptors (MC4-Rs) in brain nuclei associated with food intake profoundly influences consummatory behavior. Of these nuclei, the dorsal motor vagal nucleus (DMV), which has a dense concentration of MC4-Rs, is an important regulator of gastric tone and motility. Hence, the present study sought to examine the role of MC4-Rs in this nucleus on these activities. Using an in vivo approach, MC4-R agonists, melanotan-II (MT-II) or a-melanocyte stimulating hormone (a-MSH), were unilaterally microinjected into the DMV of rats, and their effects were noted on gastric activity. MT-II decreased phasic contractions, whereas a-MSH increased their amplitude. Both effects were blocked by the MC4-R antagonist SHU9119 or by ipsilateral vagotomy. Microinjection of the agonists (MT-II and a-MSH) into the overlying nucleus of the solitary tract (NTS), an important component of "vago-vagal" gastric circuitry, decreased phasic contractions. In addition, a-MSH reduced gastric tone and mean arterial blood pressure. To study the underlying mechanisms of the effect of MC4-R stimulation on gastric activity, electrophysiological recordings were made from labeled DMV antrum neurons in rat pups and MC4-R-/- mice. Bath application of MT-II or a-MSH significantly reduced spontaneous action potentials (but not in MC4-R-/- mice). However, in low-calcium ACSF, MT-II decreased neuronal firing, whereas a-MSH increased it. These effects mirror those of our in vivo DMV studies. Altogether, our novel findings show that activation of MC4-Rs in the brainstem, particularly in the medial NTS by the endogenous peptide a-MSH, modulates gastric activity, which may have physiological relevance for food intake and gastric function.
- Subjects
BRAIN stem; MELANOCORTIN receptors; CELLULAR signal transduction; VAGUS nerve; CELL motility; NEUROPHYSIOLOGY
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 33, p13286
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0780-13.2013