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Characterization of the effects of cannabinoids on guinea-pig tracheal smooth muscle tone: role in the modulation of acetylcholine release from parasympathetic nerves.

Abstract：

:We investigated the ability of the cannabinoid agonists CP55,940 (CB(1)/CB(2)) and anandamide (endogenous cannabinoid) to modulate electrical field stimulation (EFS)-induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea-pig trachea. We assessed whether modulation of transmitter release translated to an impact on functional responses by investigating the effect of these agents on contractile responses evoked by EFS and ACh. Furthermore, we evaluated the ability of these compounds to elicit bronchodilation in pre-contracted guinea-pig tracheal strips. CP55,940 and anandamide significantly inhibited EFS-evoked ACh release (maximal inhibition of 35.1+/-2.9% and 33.4+/-6.4% at 1 microM, P<0.05, respectively). The CB(1) receptor antagonist SR 141716A (1 microM), had no effect on ACh release and failed to reverse the inhibitory effect of CP55,940 (1 microM). Paradoxically, CP55,940 had no significant effect on EFS-evoked cholinergic contractile responses. Furthermore, CP55,940 did not relax pre-contracted tracheal strips or affect contractile responses to exogenous ACh. This lack of activity on smooth muscle tone is consistent with the fact that no detectable specific binding of [(3)H] CP55,940 was found in tracheal homogenates. These data suggest that cannabinoid agonists inhibit ACh release from cholinergic nerve terminals via activation of CB(2) receptors but that this inhibitory action does not impact on functional responses such as cholinergic contraction.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Spicuzza L,Haddad EB,Birrell M,Ling A,Clarke D,Venkatesan P,Barnes PJ,Belvisi MG

doi

10.1038/sj.bjp.0703497

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

1720-6

issue

7

eissn

0007-1188

issn

1476-5381

journal_volume

130

pub_type

杂志文章

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