N-arachidonyl dopamine sensitizes rat capsaicin-sensitive lung vagal afferents via activation of TRPV1 receptors.
We investigated the effect of N-arachidonyl dopamine (NADA), an endogenous agonist of both transient receptor potential vanilloid 1 (TRPV1) and cannabinoid CB1 receptors, on the sensitivity of rat capsaicin-sensitive lung vagal afferent (CSLVA) fibers. In artificially ventilated rats, an intravenous infusion of NADA (400 microg/kg/ml, 0.5 ml/min for 2 min) mildly elevated the baseline CSLVA fiber activity, whereas it markedly potentiated CSLVA fiber responses to a right atrial injection of capsaicin or adenosine, and to lung inflation. The potentiating effect on CSLVA fiber sensitivity to an adenosine injection or lung inflation was blocked by capsazepine pretreatment (a TRPV1 receptor antagonist), but was unaffected by AM251 pretreatment (a CB1 receptor antagonist). In spontaneously breathing rats, a NADA infusion similarly potentiated the CSLVA fiber-mediated apneic response evoked by an adenosine injection, and this potentiating effect was also prevented by capsazepine pretreatment. We concluded that NADA at the dose tested non-specifically increases CSLVA fiber sensitivity to chemical and mechanical stimulation via activation of TRPV1 receptors.
Hsu
Chun-Chun
CC
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Bien
Mauo-Ying
MY
Huang
Ya Tien
YT
Ruan
Ting
T
Kou
Yu Ru
YR
Lin
You Shuei
YS
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000187:drug effects; D050916:TRPV Cation Channels / Q000819:agonists*; D014630:Vagus Nerve / Q000187:drug effects*
D001095:Arachidonic Acids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C474941:arachidonyl dopamine; C103505:AM 251; D000241:Adenosine; D002211:Capsaicin; D004298:Dopamine