Calcium transient evoked by nicotine in isolated rat vagal pulmonary sensory neurons.
It has been shown that inhaled cigarette smoke activates vagal pulmonary C fibers and rapidly adapting receptors (RARs) in the airways and that nicotine contained in the smoke is primarily responsible. This study was carried out to determine whether nicotine alone can activate pulmonary sensory neurons isolated from rat vagal ganglia; the response of these neurons was determined by fura-2-based ratiometric Ca(2+) imaging. The results showed: 1) Nicotine (10(-4) M, 20 s) evoked a transient increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in 175 of the 522 neurons tested (Delta[Ca(2+)](i) = 142.2 +/- 12.3 nM); the response was reproducible, with a small reduction in peak amplitude in the same neurons when the challenge was repeated 20 min later. 2) A majority (59.7%) of these nicotine-sensitive neurons were also activated by capsaicin (10(-7) M). 3) 1,1-Dimethyl-4-phenylpiperazinium iodide (DMPP; 10(-4) M, 20 s), a selective agonist of the neuronal nicotinic acetylcholine receptors (NnAChRs), evoked a pattern of response similar to that of nicotine. 4) The responses to nicotine and DMPP were either totally abrogated or markedly attenuated by hexamethonium (10(-4) M). 5) In anesthetized rats, right atrial bolus injection of nicotine (75-200 mug/kg) evoked an immediate (latency <1-2 s) and intense burst of discharge in 47.8% of the pulmonary C-fiber endings and 28.6% of the RARs tested. In conclusion, nicotine exerts a direct stimulatory effect on vagal pulmonary sensory nerves, and the effect is probably mediated through an activation of the NnAChRs expressed on the membrane of these neurons.
Xu
Jennings
J
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Yang
Wenbin
W
Zhang
Guangfan
G
Gu
Qihai
Q
Lee
Lu-Yuan
LY
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity; D008168:Lung / Q000187:drug effects* / Q000294:innervation* / Q000503:physiopathology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009620:Nodose Ganglion / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012907:Smoking / Q000009:adverse effects / Q000503:physiopathology; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology
D005731:Ganglionic Stimulants; D007509:Irritants; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine