OPIOIDS MODULATE THE CHOLINERGIC CONTRACTION BUT NOT THE NONADRENERGIC RELAXATION IN GUINEA-PIG AIRWAYS IN-VITRO

D-ALa(2), NMePhe(4), Gly-ol(5)) encephalin (DAMGO), a selective mu-opi oid receptor agonist, has previously been demonstrated to inhibit the cholinergic and the noncholinergic contraction in guinea-pig airways, In contrast, opioids had no inhibitory effect on cholinergic neurotran smission in the upper trachea when stimulated at 8 Hz. We investigated whether DAMGO, a selective mu-opioid receptor agonist, [D-Pen(2,5)] e ncephalin (DPDPE), a selective delta-opioid receptor agonist, and U-69 593, a selective kappa-opioid receptor agonist could modulate the chol inergic contraction in the upper trachea at different frequencies of s timulation, Moreover, we have investigated whether DAMGO, DPDPE and U- 69593 could also modulate the iNANC relaxation. DAMGO (1-100 mu M) inh ibited the cholinergic contraction in the upper trachea with a maximum inhibition of 57+/-15% at 1 Hz (n=4; p<0.05). On the other hand, DPDP E (10 mu M) and U69593 (10 mu M) did not produce any significant inhib ition of the cholinergic contraction, Naloxone, an opioid receptor ant agonist (100 mu M), was able to antagonize the inhibitory effect of DA MGO (n=5; p<0.01) on the cholinergic contraction at a frequency of 2 H z, DAMGO (10 mu M) did not displace the cumulative concentration-respo nse relationship to acetylcholine (10 nM-10 mM), (n=4; NS). This provi des evidence that prejunctional mu-opioid receptors (and not delta-opi oid or kappa-opioid receptors) modulate cholinergic contraction in the upper trachea, In contrast, DAMGO (10 mu M) had no significant inhibi tory effect on the nonadrenergic relaxation (n=4; NS) in the upper tra chea, Neither DPDPE nor U69593 had any effect on the nonadrenergic rel axation. These findings suggest that DAMGO directly inhibits the choli nergic contraction and that the opioid receptor involved in the inhibi tion of the cholinergic contraction in the upper trachea is of the mu- opioid type. The finding that opioids inhibit cholinergic contraction without altering NANC relaxations suggests that distinct populations o f nerves mediate these two effects.