Modulation of the release of endogenous adenosine by cannabinoids in the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum.

1 Interactions between the cannabinoid system and the adenosine system were investigated in the myenteric plexus-longitudinal muscle (MPLM) of the guinea-pig ileum. 2 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 effect were reversed by the selective A[SUB1] receptor antagonist DPCPX (20 nM). 3 Preincubation of the MPLM with the cannabinoid receptor agonist CP55,940 (1 nM) or the endogenous cannabinoid ligand anandamide caused a significant leftward shift in the concentration-effect curves to adenosine and 2-chloroadenosine. 4 Electrically-evoked contractions of the MPLM were inhibited in a concentration dependent manner by the adenosine uptake inhibitor dipyridamole. The inhibition was reversed by DPCPX (20 nM). 5 Pretreatment with CP55,940 (1 nM) or anandamide (10 μM) significantly reduced the inhibition produced by dipyridamole, an effect which was completely reversed by the selective CB[SUB1] receptor ligand SR 141716 (100 nM). 6 Electrically evoked adenosine release, measured in real time by means of adenosine-specific biosensors, was inhibited by CP55,940 (10 nM). This inhibition was blocked when CP55,940 was applied in the presence of SR141716 (100 nM). 7 These results confirm the presence of presynaptic CB[SUB1] and A[SUB1] receptors in the guinea-pig MPLM, and suggest that CB[SUB1] receptor stimulation reduces electrically-evoked adenosine release. Overall the date raise the possibility that the cannabinoid system plays a role in the modulation of adenosine transmission in the MPLM. [ABSTRACT FROM AUTHOR]