Modulation of cholinergic neurotransmission in guinea‐pig trachea by neuropeptide Y

1 Neuropeptide Y (NPY) is localized to adrenergic nerves in guinea‐pig airways but its function is not known. 2 NPY (1 × 10−10‐3 × 10−7 m) had no direct effect on guinea‐pig tracheal smooth muscle in vitro. 3 NPY produced a concentration‐ and frequency‐dependent inhibition of the cholinergic component of responses elicited by electrical field stimulation (EFS) whilst having no effect on the contractile response to exogenously applied acetylcholine (ACh). 4 Yohimbine was able to reverse significantly the inhibitory effect of noradrenaline on the cholinergic component to EFS without having any significant effect on the inhibition produced by NPY. 5 Neither blockade of β‐adrenoceptors by propranolol, nor depletion of adrenergic nerves by incubation with 6‐hydroxydopamine caused any significant alteration in the response to EFS in the presence of 3 × 10−7 m NPY. Bretylium tosylate incubation to prevent noradrenaline release produced a small but significant enhancement of the inhibitory effect of NPY on EFS at high frequencies. 6 NPY appears to reduce the cholinergic component to EFS via a prejunctional mechanism, acting directly on receptors on cholinergic nerve terminals, rather than affecting adrenergic mechanisms. NPY released by adrenergic nerves may modulate cholinergic neurotransmission in guinea‐pig airways.