title: Tumor necrosis factor potentiates central vagal afferent signaling by modulating ryanodine channels.
abstract: Disease processes such as infection, leukemia, and autoimmune disorders are often associated with nausea, emesis, and anorexia. A common denominator of these rather disparate states is the production of the early, proinflammatory cytokine tumor necrosis factor-alpha (TNF) in significant quantities. Recent studies have shown that TNF may act as a neuromodulator in the hindbrain to produce malaise by potentiating visceral afferent signaling at the central processes of the vagus nerve. However, the mechanism by which TNF produces this signal amplification is not known. Our time-lapse calcium imaging studies of individual central vagal afferent varicosities in the caudal brainstem slice preparation show that, although TNF has minimal direct effects to elevate terminal intracellular calcium levels, TNF does potentiate the terminal afferent responses to other stimuli through a ryanodine-based, calcium-induced calcium release mechanism. Such a scheme may explain how TNF sensitizes visceral as well as somatosensory primary afferents.
authors.affiliation: Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. rogersrc@pbrc.edu
authors.forename: Richard C
authors.initials: RC
authors.lastname: Rogers
authors.forename: Montina J
authors.initials: MJ
authors.lastname: Van Meter
authors.forename: Gerlinda E
authors.initials: GE
authors.lastname: Hermann
mesh_terms: D000344:Afferent Pathways / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000502:physiology; D005260:Female; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014630:Vagus Nerve / Q000378:metabolism / Q000502:physiology*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium