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Modulation of the release of endogenous adenosine by cannabinoids in the myenteric plexus‐longitudinal muscle preparation of the guinea‐pig ileum
Author(s) -
Begg M,
Dale N,
Llaudet E,
Molleman A,
Parsons M E
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704985
Subject(s) - adenosine , cannabinoid receptor , agonist , adenosine a1 receptor , cannabinoid , myenteric plexus , adenosine receptor , adenosine a3 receptor , pharmacology , medicine , endocrinology , cannabinoid receptor type 2 , purinergic signalling , depolarization induced suppression of inhibition , chemistry , cgs 21680 , biology , receptor , immunohistochemistry
Interactions between the cannabinoid system and the adenosine system were investigated in the myenteric plexus‐longitudinal muscle (MPLM) of the guinea‐pig ileum. Electrically‐evoked contractions of the MPLM were inhibited in a concentration dependent manner by exogenous adenosine and the adenosine receptor agonist 2‐chloroadenosine. These inhibitory effects were reversed by the selective A 1 receptor antagonist DPCPX (20 n M ). Preincubation of the MPLM with the cannabinoid receptor agonist CP55,940 (1 n M ) or the endogenous cannabinoid ligand anandamide caused a significant leftward shift in the concentration‐effect curves to adenosine and 2‐chloroadenosine. Electrically‐evoked contractions of the MPLM were inhibited in a concentration dependent manner by the adenosine uptake inhibitor dipyridamole. This inhibition was reversed by DPCPX (20 n M ). Pretreatment with CP55,940 (1 n M ) or anandamide (10 μ M ) significantly reduced the inhibition produced by dipyridamole, an effect which was completely reversed by the selective CB 1 receptor ligand SR141716 (100 n M ). Electrically evoked adenosine release, measured in real time by means of adenosine‐specific biosensors, was inhibited by CP55,940 (10 n M ). This inhibition was blocked when CP55,940 was applied in the presence of SR141716 (100 n M ). These results confirm the presence of presynaptic CB 1 and A 1 receptors in the guinea‐pig MPLM, and suggest that CB 1 receptor stimulation reduces electrically‐evoked adenosine release. Overall the data raise the possibility that the cannabinoid system plays a role in the modulation of adenosine transmission in the MPLM.British Journal of Pharmacology (2002) 137 , 1298–1304. doi: 10.1038/sj.bjp.0704985