Inhibition of cholinergic and non-adrenergic, non-cholinergic bronchoconstriction in the guinea pig mediated by neuropeptide Y and alpha 2-adrenoceptors and opiate receptors.

The mechanisms underlying the regulatory influence of neuropeptide Y (NPY) and of alpha 2-adrenoceptor and opiate receptor activation on cholinergic and excitatory non-adrenergic, non-cholinergic (e-NANC) neurotransmission were studied in guinea pig hilus bronchi in vitro. NPY inhibited both the cholinergic and e-NANC bronchial contractions evoked by field stimulation. The NPY attenuation of the e-NANC contraction could not be antagonized by the alpha 2-antagonist, idazoxan, or naloxone. UK 14,304 a specific alpha 2-agonist, also reduced the two nervous components of bronchial contraction and this action was inhibited by idazoxan. NPY and UK 14,304 exerted a minor influence on the bronchial smooth muscle tone per se or on contractions evoked by acetylcholine or neurokinin A. This suggested that the inhibitory responses were caused by a prejunctional action reducing the release of transmitter substances from sensory and cholinergic nerve endings. Furthermore NPY (10(-7) M) seemed to be more potent to inhibit both contractile components than noradrenaline (10(-6) M) in the presence of propranolol (3 X 10(-6) M). Morphine was able to reduce the e-NANC response via a naloxone-sensitive mechanism. The capsaicin-evoked bronchoconstriction and the bronchodilator NANC effect evoked by field stimulation were, however, not influenced by UK 14,304. It is concluded that NPY, alpha 2-receptor and opiate receptor activation inhibit the release of sensory transmitters evoked by field stimulation but not by capsaicin.