title: Central vagal afferent endings mediate reduction of food intake by melanocortin-3/4 receptor agonist.
abstract: Injection of the melanocortin-3/4 receptor agonist melanotan-II (MTII) into the nucleus of the solitary tract (NTS) produces rapid and sustained reduction of food intake. Melanocortin-4 receptors (MC4Rs) are expressed by vagal afferent endings in the NTS, but it is not known whether these endings participate in MTII-induced reduction of food intake. In experiments described here, we evaluated the contribution of central vagal afferent endings in MTII-induced reduction of food intake. Examination of rat hindbrain sections revealed that neuronal processes expressing immunoreactivity for the endogenous MC4R agonist α-melanoctyte-stimulating hormone course parallel and wrap around anterogradely labeled vagal afferent endings in the NTS and thus are aptly positioned to activate vagal afferent MC4Rs. Furthermore, MTII and endogenous MC4R agonists increased protein kinase A (PKA)-catalyzed phosphorylation of synapsin I in vagal afferent endings, an effect known to increase synaptic strength by enhancing neurotransmitter release in other neural systems. Hindbrain injection of a PKA inhibitor, KT5720, significantly attenuated MTII-induced reduction of food intake and the increase in synapsin I phosphorylation. Finally, unilateral nodose ganglion removal, resulting in degeneration of vagal afferent endings in the ipsilateral NTS, abolished MTII-induced synapsin I phosphorylation ipsilateral to nodose ganglion removal. Moreover, reduction of food intake following MTII injection into the NTS ipsilateral to nodose ganglion removal was significantly attenuated, whereas the response to MTII was not diminished when injected into the contralateral NTS. Altogether, our results suggest that reduction of food intake following hindbrain MC4R activation is mediated by central vagal afferent endings.
authors.affiliation: Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164 carloscampos@vetmed.wsu.edu.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Campos
authors.affiliation: Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shiina
authors.affiliation: Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Ritter
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009411:Nerve Endings / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology; D016704:Synapsins / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D044105:Receptor, Melanocortin, Type 4; D016704:Synapsins; C079282:melanotan-II; D000521:alpha-MSH; C057416:KT 5720
keywords: gastrointestinal; hindbrain; satiation