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Adenosine A 1  and cannabinoid CB 1  receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A 1  and CB 1  receptors modulates cAMP accumulation in rat hippocampal slices. The CB 1  agonist WIN55212-2 (0.3–30  μ M) decreased forskolin-stimulated cAMP accumulation with an EC 50  of 6.6 ± 2.7  μ M and an  E   max⁡  of 31% ± 2%, whereas for the A 1  agonist, N 6 -cyclopentyladenosine (CPA, 10–150 nM), an EC 50  of 35 ± 19 nM, and an  E   max⁡  of 29% ± 5 were obtained. The combined inhibitory effect of WIN55212-2 (30  μ M) and CPA (100 nM) on cAMP accumulation was 41% ± 6% ( n  = 4), which did not differ ( P  > 0.7) from the sum of the individual effects of each agonist (43% ± 8%) but was different ( P  < 0.05) from the effects of CPA or WIN55212-2 alone. Preincubation with CPA (100 nM) for 95 min caused desensitization of adenosine A 1  activity, which did not modify the effect of WIN55212-2 (30  μ M) on cAMP accumulation. In conclusion, the combined effect of CB 1  and A 1  receptors on cAMP formation is additive and CB 1  receptor activity is not affected by short-term A 1  receptor desensitization.

biomed research international

The Combined Inhibitory Effect of the Adenosine A1and Cannabinoid CB1Receptors on cAMP Accumulation in the Hippocampus Is Additive and Independent of A1Receptor Desensitization