Inhibition of cholinergic neurotransmission in human airways by opioids.

Autor: Belvisi MG; Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom., Stretton CD, Verleden GM, Ledingham SJ, Yacoub MH, Barnes PJ
Jazyk: angličtina
Zdroj: Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 1992 Mar; Vol. 72 (3), pp. 1096-100.
DOI: 10.1152/jappl.1992.72.3.1096
Abstrakt: Opioids reduce the cholinergic responses to electrical field stimulation (EFS) in guinea pig and canine airways by a prejunctional effect. We determined whether a similar effect operates in human airways in vitro. [D-Ala2-NMePhe4-Gly-ol5]enkephalin (DAMGO) (10(-8)-10(-6) M), a selective mu-opioid receptor agonist, inhibited the response to EFS in a dose- and frequency-dependent manner. DAMGO (10(-6) M) produced 86% inhibition at 0.5 Hz and 38% inhibition at 4 Hz, but at 32 Hz there was no significant inhibition. Another selective mu-opioid receptor agonist H-Tyr-D-Arg-Gly-Phe(4-NO2)-Pro-NH2 diacetate (BW 443C) also inhibited responses to EFS, producing 57.7% inhibition at 4 Hz at a concentration of 10(-6) M. The inhibitory effect on EFS was blocked by the opioid receptor antagonist naloxone (10(-5) M), indicating that opioid receptors are involved. DAMGO (10(-6) M) had no effect on the contractile response to exogenous acetylcholine, indicating a prejunctional effect. We conclude that mu-opioid agonists inhibit cholinergic neurotransmission in human airways in vitro, and this could have therapeutic potential in the treatment of airway disease.
Databáze: MEDLINE