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.
Matran
R
R
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Martling
C R
CR
Lundberg
J M
JM
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects*; D000068438:Brimonidine Tartrate; D001980:Bronchi / Q000187:drug effects; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D009478:Neuropeptide Y / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D013566:Sympathomimetics / Q000494:pharmacology
D000959:Antihypertensive Agents; D009478:Neuropeptide Y; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D013566:Sympathomimetics; D000068438:Brimonidine Tartrate; D009020:Morphine