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Modulation of cholinergic neurotransmission in guinea-pig airways by opioids.
Br J Pharmacol. 1990 May; 100(1):131-7.BJ

Abstract

1. Opioid receptors have been localised on sensory fibres in the vagus nerve and opioids have previously been shown to inhibit non-adrenergic, non-cholinergic (NANC) neurotransmission in guinea-pig bronchi in vitro and in vivo. We have now investigated whether an inhibitory effect could be demonstrated on cholinergic neurotransmission. 2. Electrical field stimulation (EFS) (8 Hz, 0.5 ms, 40 V for 20 s) produced only a rapid, cholinergic response in the upper trachea but in the lower trachea and main bronchi a cholinergic response which was atropine-sensitive and a longer lasting NANC contraction that was atropine-insensitive was demonstrated. This slow contraction could be blocked by tetrodotoxin and capsaicin pretreatment. 3. [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAMGO), a selective mu-opioid receptor agonist, inhibited the cholinergic response to EFS at 8 Hz in a dose-dependent manner in main bronchi (IC50 = 113 nM with a maximal inhibition of 35.7 +/- 5.6% 10 microM, n = 5). In the lower trachea, DAMGO inhibited the cholinergic response to a similar extent (inhibition of 35.8 +/- 3.5% at 10 microM, n = 5). However, DAMGO had no effect on the contractile response to exogenously applied acetylcholine in the main bronchi. By contrast, opioids had no inhibitory effect on cholinergic neurotransmission in the upper trachea. DAMGO (1 microM) inhibited the cholinergic response to EFS in a frequency-dependent manner in the main bronchi with greater inhibition at lower frequencies of stimulation. 4. The delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) significantly inhibited the cholinergic component of the constrictor response to EFS at 8 Hz in the bronchi but at the highest dose used (10 microM). U-50,488H, a Kappa-receptor agonist, had no inhibitory effect on the cholinergic constrictor component in the main bronchi (10microM). 5. DAMGO also inhibited the NANC responses to EFS in the main bronchi in a dose-dependent manner (with an IC50 = 36 nm and a maximal inhibition of 63.4 + 8.3%, at 1 microM, n = 5). DAMGO had no effect on contractile responses to exogenously applied substance P (SP). DPDPE (10 microM) was less effective in inhibition of the NANC bronchoconstriction with a maximal inhibition of 29.2 + 4.2% (n = 7), and U-50,488H (1O microM) had no inhibitory effect. 6. After capsaicin pretreatment, which depleted sensory nerves of neuropeptides, the inhibitory effect of DAMGO (1 microM) on cholinergic constriction in main bronchi at 8 Hz was only 13.4 + 1.9% (n = 13) compared with 32.9 + 4.0% (n = 9) inhibition in vehicle-treated controls (P < 0.001). 7. Opioids may reduce the cholinergic neural responses in airways partly via an inhibitory action on excitatory NANC nerves and partly by a direct effect on cholinergic neurotransmission. The opioid receptor involved is of the mu-opioid receptor subtype.

Authors+Show Affiliations

Department of Thoracic Medicine, National Heart and Lung Institute, London.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1695531

Citation

Belvisi, M G., et al. "Modulation of Cholinergic Neurotransmission in Guinea-pig Airways By Opioids." British Journal of Pharmacology, vol. 100, no. 1, 1990, pp. 131-7.
Belvisi MG, Stretton CD, Barnes PJ. Modulation of cholinergic neurotransmission in guinea-pig airways by opioids. Br J Pharmacol. 1990;100(1):131-7.
Belvisi, M. G., Stretton, C. D., & Barnes, P. J. (1990). Modulation of cholinergic neurotransmission in guinea-pig airways by opioids. British Journal of Pharmacology, 100(1), 131-7.
Belvisi MG, Stretton CD, Barnes PJ. Modulation of Cholinergic Neurotransmission in Guinea-pig Airways By Opioids. Br J Pharmacol. 1990;100(1):131-7. PubMed PMID: 1695531.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of cholinergic neurotransmission in guinea-pig airways by opioids. AU - Belvisi,M G, AU - Stretton,C D, AU - Barnes,P J, PY - 1990/5/1/pubmed PY - 1990/5/1/medline PY - 1990/5/1/entrez SP - 131 EP - 7 JF - British journal of pharmacology JO - Br J Pharmacol VL - 100 IS - 1 N2 - 1. Opioid receptors have been localised on sensory fibres in the vagus nerve and opioids have previously been shown to inhibit non-adrenergic, non-cholinergic (NANC) neurotransmission in guinea-pig bronchi in vitro and in vivo. We have now investigated whether an inhibitory effect could be demonstrated on cholinergic neurotransmission. 2. Electrical field stimulation (EFS) (8 Hz, 0.5 ms, 40 V for 20 s) produced only a rapid, cholinergic response in the upper trachea but in the lower trachea and main bronchi a cholinergic response which was atropine-sensitive and a longer lasting NANC contraction that was atropine-insensitive was demonstrated. This slow contraction could be blocked by tetrodotoxin and capsaicin pretreatment. 3. [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAMGO), a selective mu-opioid receptor agonist, inhibited the cholinergic response to EFS at 8 Hz in a dose-dependent manner in main bronchi (IC50 = 113 nM with a maximal inhibition of 35.7 +/- 5.6% 10 microM, n = 5). In the lower trachea, DAMGO inhibited the cholinergic response to a similar extent (inhibition of 35.8 +/- 3.5% at 10 microM, n = 5). However, DAMGO had no effect on the contractile response to exogenously applied acetylcholine in the main bronchi. By contrast, opioids had no inhibitory effect on cholinergic neurotransmission in the upper trachea. DAMGO (1 microM) inhibited the cholinergic response to EFS in a frequency-dependent manner in the main bronchi with greater inhibition at lower frequencies of stimulation. 4. The delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) significantly inhibited the cholinergic component of the constrictor response to EFS at 8 Hz in the bronchi but at the highest dose used (10 microM). U-50,488H, a Kappa-receptor agonist, had no inhibitory effect on the cholinergic constrictor component in the main bronchi (10microM). 5. DAMGO also inhibited the NANC responses to EFS in the main bronchi in a dose-dependent manner (with an IC50 = 36 nm and a maximal inhibition of 63.4 + 8.3%, at 1 microM, n = 5). DAMGO had no effect on contractile responses to exogenously applied substance P (SP). DPDPE (10 microM) was less effective in inhibition of the NANC bronchoconstriction with a maximal inhibition of 29.2 + 4.2% (n = 7), and U-50,488H (1O microM) had no inhibitory effect. 6. After capsaicin pretreatment, which depleted sensory nerves of neuropeptides, the inhibitory effect of DAMGO (1 microM) on cholinergic constriction in main bronchi at 8 Hz was only 13.4 + 1.9% (n = 13) compared with 32.9 + 4.0% (n = 9) inhibition in vehicle-treated controls (P < 0.001). 7. Opioids may reduce the cholinergic neural responses in airways partly via an inhibitory action on excitatory NANC nerves and partly by a direct effect on cholinergic neurotransmission. The opioid receptor involved is of the mu-opioid receptor subtype. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/1695531/Modulation_of_cholinergic_neurotransmission_in_guinea_pig_airways_by_opioids_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0007-1188&amp;date=1990&amp;volume=100&amp;issue=1&amp;spage=131 DB - PRIME DP - Unbound Medicine ER -