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Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids.
J Neurosci 2012; 32(15):5237-41JN

Abstract

The early proinflammatory cytokine tumor necrosis factor (TNF) is released in significant quantities by the activated immune system in response to infection, leukemia, autoimmune disorders, and radiation sickness. Nausea, emesis, and anorexia are common features of these disorders. TNF action on vagal afferent terminals in the brainstem is a likely cause of the malaise associated with these disorders. Our previous work has shown that TNF action to excite vagal afferents occurs as a result of sensitization of ryanodine channels in afferent nerve terminals. For millennia, cannabinoids (CB) have been used to combat the visceral malaise associated with chronic disease, although the mechanism of action has not been clear. Previous work in culture systems suggests that CB1 agonists can suppress neurotransmission by downregulating ryanodine channels through a protein kinase A (PKA)-dependent mechanism. Laser confocal calcium imaging methods were used to directly examine effects of CB1 cannabinoid agonists and TNF on visceral afferent signaling in the rat hindbrain. CB1 agonists blocked the effects of TNF to amplify vagal afferent responsiveness; blockade of PKA with H89 also eliminated the TNF amplification effect. These results help to explain the effectiveness of cannabinoids in blocking the malaise generated by TNF-releasing disease processes by opposing effects on ryanodine channels.

Authors+Show Affiliations

Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22496569

Citation

Rogers, Richard C., and Gerlinda E. Hermann. "Tumor Necrosis Factor Activation of Vagal Afferent Terminal Calcium Is Blocked By Cannabinoids." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 32, no. 15, 2012, pp. 5237-41.
Rogers RC, Hermann GE. Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. J Neurosci. 2012;32(15):5237-41.
Rogers, R. C., & Hermann, G. E. (2012). Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 32(15), pp. 5237-41. doi:10.1523/JNEUROSCI.6220-11.2012.
Rogers RC, Hermann GE. Tumor Necrosis Factor Activation of Vagal Afferent Terminal Calcium Is Blocked By Cannabinoids. J Neurosci. 2012 Apr 11;32(15):5237-41. PubMed PMID: 22496569.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. AU - Rogers,Richard C, AU - Hermann,Gerlinda E, PY - 2012/4/13/entrez PY - 2012/4/13/pubmed PY - 2012/6/16/medline SP - 5237 EP - 41 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 32 IS - 15 N2 - The early proinflammatory cytokine tumor necrosis factor (TNF) is released in significant quantities by the activated immune system in response to infection, leukemia, autoimmune disorders, and radiation sickness. Nausea, emesis, and anorexia are common features of these disorders. TNF action on vagal afferent terminals in the brainstem is a likely cause of the malaise associated with these disorders. Our previous work has shown that TNF action to excite vagal afferents occurs as a result of sensitization of ryanodine channels in afferent nerve terminals. For millennia, cannabinoids (CB) have been used to combat the visceral malaise associated with chronic disease, although the mechanism of action has not been clear. Previous work in culture systems suggests that CB1 agonists can suppress neurotransmission by downregulating ryanodine channels through a protein kinase A (PKA)-dependent mechanism. Laser confocal calcium imaging methods were used to directly examine effects of CB1 cannabinoid agonists and TNF on visceral afferent signaling in the rat hindbrain. CB1 agonists blocked the effects of TNF to amplify vagal afferent responsiveness; blockade of PKA with H89 also eliminated the TNF amplification effect. These results help to explain the effectiveness of cannabinoids in blocking the malaise generated by TNF-releasing disease processes by opposing effects on ryanodine channels. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/22496569/abstract/Tumor_necrosis_factor_activation_of_vagal_afferent_terminal_calcium_is_blocked_by_cannabinoids L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=22496569 DB - PRIME DP - Unbound Medicine ER -