To evaluate the functional status of neuronal ₂-adrenoceptors (ARs) and ₂-ARs on ACh release in horses with recurrent airway obstruction (RAO), we examined the effects of the physiological agonists epinephrine (Epi) and norepinephrine (NE) and the ₂-agonists RR- and RR/SS-formoterol on ACh release from airway cholinergic nerves of horses with RAO. Because SS-formoterol, a distomer of the ₂-agonist, increases ACh release from airways of control horses only after the autoinhibitory muscarinic receptors are blocked by atropine, we also tested the hypothesis that if there is an M₂-receptor dysfunction in equine RAO, SS-formoterol should increase ACh release even in the absence of atropine. ACh release was evoked by electrical field stimulation and measured by HPLC. Epi and NE caused less inhibition of ACh release in horses with RAO than in control horses. At the catecholamine concentration achieved during exercise (10⁷ M), the inhibition induced by Epi and NE was 10.8 ± 13.2 and 3.4 ± 6.8%, respectively, in equine RAO versus 41.0 ± 6.4 and 27.1 ± 5.6%, respectively, in control horses. RR- and RR/SS-formoterol (10⁸ to 10⁵ M) increased ACh release to a similar magnitude as that in control horses. These results indicate that neuronal ₂-ARs are functioning; however, the ₂-ARs are dysfunctional in the airways of horses with RAO in response to circulating catecholamines. SS-formoterol (10⁸ to 10⁵ M) facilitated ACh release in horses with RAO even in the absence of atropine. Addition of atropine did not cause significantly more augmentation of ACh release over the effect of SS-formoterol alone. The magnitude of augmentation in horses with RAO in the absence of atropine was similar to that in control horses in the presence of atropine. The latter observations could be explained by neuronal muscarinic-autoreceptor dysfunction in equine RAO.

adrenoceptor; prejunctional; muscarinic receptor; catecholamine; formoterol; enantiomer; autoreceptor

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