ATP causes neurogenic bronchoconstriction in the dog

Abstract

Adenosine 5′‐triphosphate (ATP) causes bronchoconstriction in normal and asthmatic human subjects. The mechanism of this action is not known. Because ATP is known to elicit vagal afferent neural traffic by stimulating pulmonary vagal C‐fiber terminals, we have hypothesized that this action of ATP results in reflex bronchoconstriction. To test this hypothesis, ATP, adenosine, and capsaicin were administered as rapid boluses into the right atrium of anesthetized dogs (n = 8) before and after either atropine or bilateral cervical vagotomy. ATP and adenosine were given also in the presence of physostigmine to accentuate vagal input into the lungs. Fluoroscopic visualization of the bronchial tree was achieved by insufflation of heavy metal powder into the lungs. Bronchi diameters were determined using bronchograms. Pulmonary dynamics were quantitated using tracheal and esophageal pressures and respiratory air flow. ATP, adenosine, and capsaicin caused bronchoconstriction that was eliminated by either atropine or vagotomy. The effect of ATP was much more pronounced (P < 0.05) than that of adenosine and capsaicin: the diameter of generation III bronchi of 6.8 ± 0.8 mm was reduced by 27.5 ± 2.1%, 10.0 ± 2.1%, and 15.4 ± 3.3% by ATP, adenosine, and capsaicin, respectively. Similarly, in the presence of physostigmine, lung resistance of 2.67 ± 0.24 mmH2O/l per min and 2.76 ± 0.20 was increase by 68 ± 25% and 16 ± 12% by ATP and adenosine, respectively (P < 0.05). Because endogenous ATP is released into the extracellular space under physiologic and pathophysiologic conditions, the present data indicated that endogenous ATP could trigger neurogenic bronchoconstriction and thereby play a mechanistic role in obstructive airway diseases in general and asthma in particular. Drug Dev. Res. 45:342–349, 1998. © 1998 Wiley‐Liss, Inc.

Purinergic Signaling in the Airways

“…Sensory Nerves, Reflex Activity, and Pain. In canine lungs, ATP activates pulmonary vagal C fiber sensory nerve terminals, mediated by P2X receptors (Pelleg and Hurt, 1996), and causes reflex bronchoconstriction (Katchanov et al, 1998). In another study, activation of P2X receptors on vagal afferent terminals evoked Bezold-Jarisch depressor cardiorespiratory reflexes in anesthetized rats (McQueen et al, 1998).…”

Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. V. Role of purinergic receptors

“…The ability of P2XR agonists to induce C fiber-dependent nociception has already been demonstrated (9). Whether this action of ATP on pulmonary C fiber nerve terminals is responsible for neurogenic (i.e., vagal dependent) bronchoconstriction induced by ATP (14) remains to be determined because ATP can also stimulate the pulmonary rapidly adapting receptors of afferent A␦ fibers (A. Pelleg and C. Hurt, unpublished observations). The ability of ATP to stimulate both capsaicin-sensitive (i.e., C fibers) and capsaicin-insensitive (A␦) sensory nerve terminals is in agreement with previous observations of ATP-induced inward current in capsaicinsensitive and capsaicin-insensitive small-sized and mediumsized dorsal root ganglion neurons, respectively (31).…”

Effects of Aerosolized Adenosine 5′-Triphosphate vs Adenosine 5′-Monophosphate on Dyspnea and Airway Caliber in Healthy Nonsmokers and Patients With Asthma

“…3 Extracellular ATP can also exacerbate neurogenic bronchoconstriction and inflammation by stimulating vagal sensory nerve terminals in the lungs and stimulating the release of neuropeptides. [2][3][4] It has previously been shown that patients with asthma exhibit a more intense response (ie, bronchoconstriction) to inhaled ATP than normal individuals, and in both groups of subjects ATP was more potent than methacholine and histamine in reducing the baseline FEV 1 by 15%. 5 Adenosine is a purine nucleoside that is a product of the enzymatic degradation of ATP.…”