Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1.
Oleoylethanolamide (OEA) is an endogenous lipid that regulates feeding and body weight. Although the effects of OEA are believed to depend on activation of vagal sensory afferent neurones, the mechanisms involved in exciting these neurones are unclear. Here we show that OEA directly excited nodose ganglion neurones, the cell bodies of vagal afferents. OEA depolarized these neurones and evoked inward currents that were restricted to capsaicin-sensitive cells. These currents were fully blocked by the TRPV1 inhibitor, capsazepine, and no responses to OEA were observed in neurones cultured from TRPV1-null mice. Similarly, OEA induced a rise in Ca(+) concentration in wild-type but not TRPV1-deficient neurones, and responses to OEA were greater at 37 degrees C compared to room temperature. Significantly, OEA administration in mice induced visceral pain-related behaviours that were inhibited by capsazepine and absent in TRPV1-null animals. Further, OEA reduced 30-min food intake in wild-type but not in TRPV1-null mice. Thus, the acute behavioural effects of OEA may result from visceral malaise via the activation of TRPV1.
Wang
Xiangbin
X
Department of Pharmacology, Georgetown University, 3900 Reservoir Road NW, Washington, DC 20057, USA.
Miyares
Rosa Linda
RL
Ahern
Gerard P
GP
D000818:Animals; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D063388:Endocannabinoids; D007473:Ion Channels / Q000172:deficiency / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009620:Nodose Ganglion / Q000187:drug effects* / Q000502:physiology; D009829:Oleic Acids / Q000494:pharmacology* / Q000633:toxicity; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D050916:TRPV Cation Channels; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D014781:Viscera / Q000187:drug effects / Q000502:physiology
D063388:Endocannabinoids; D007473:Ion Channels; D009829:Oleic Acids; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C488250:oleoylethanolamide