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Nociceptin/orphanin FQ inhibits capsaicin-induced guinea-pig airway contraction through an inward-rectifier potassium channel.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2002 Feb; Vol. 135 (3), pp. 764-70. - Publication Year :
- 2002
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Abstract
- Nociceptin/orphanin FQ (N/OFQ), an endogenous opioid-like orphan receptor (NOP receptor, previously termed ORL1 receptor) agonist, has been found to inhibit capsaicin-induced bronchoconstriction in isolated guinea-pig lungs and in vivo. The underlying mechanisms are not clear. In the present studies, we tested the effect of N/OFQ on VR1 channel function in isolated guinea-pig nodose ganglia cells. Capsaicin increased intracellular Ca(2+) concentration in these cells through activation of vanilloid receptors. Capsaicin-induced Ca(2+) responses were attenuated by pretreatment of nodose neurons with N/OFQ (1 microM). N/OFQ inhibitory effect on the Ca(2+) response in nodose ganglia cells was antagonized by tertiapin (0.5 microM), an inhibitor of inward-rectifier K(+) channels, but not by verapamil, a voltage gated Ca(2+) channel blocker, indicating that an inward-rectifier K(+) channel is involved in N/OFQ inhibitory effect. In isolated guinea-pig bronchus, N/OFQ (1 microM) inhibited capsaicin-induced airway contraction. Tertiapin (0.5 microM) abolished the N/OFQ inhibition of capsaicin-induced bronchial contraction. Capsaicin (10 microg) increased pulmonary inflation pressure in the isolated perfused guinea-pig lungs. This response was significantly attenuated by pretreatment with N/OFQ (1 microM). Tertiapin also abolished the N/OFQ inhibitory effect on capsaicin-induced bronchoconstriction in perfused lungs. Capsaicin increased the release of substance P and neurokinin A from isolated lungs. N/OFQ (1 microM) blocked the capsaicin-induced tachykinin release. These results indicate that N/OFQ-induced hyperpolarization of tachykinin containing airway sensory nerves, through an inward-rectifier K(+) channel activation, accounts for the inhibition of capsaicin-evoked broncoconstriction.
- Subjects :
- Animals
Bronchi physiology
Bronchoconstriction physiology
Capsaicin antagonists & inhibitors
Guinea Pigs
In Vitro Techniques
Lung physiology
Male
Nodose Ganglion cytology
Nodose Ganglion drug effects
Nodose Ganglion physiology
Opioid Peptides pharmacology
Potassium Channels, Inwardly Rectifying agonists
Potassium Channels, Inwardly Rectifying antagonists & inhibitors
Tachykinins metabolism
Nociceptin
Bronchi drug effects
Bronchoconstriction drug effects
Capsaicin pharmacology
Lung drug effects
Opioid Peptides physiology
Potassium Channels, Inwardly Rectifying physiology
Vasoconstrictor Agents pharmacology
Vasodilator Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 135
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11834624
- Full Text :
- https://doi.org/10.1038/sj.bjp.0704515