The Combined Inhibitory Effect of the Adenosine A1 and Cannabinoid CB1 Receptors on CAMP Accumulation in the Hippocampus is Additive and Independent of A1 Receptor Desensitization

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2015 Feb 11

PMID 25667928

Citations 3

Authors

Andre Serpa

Sara Correia

Joaquim A Ribeiro

Ana M Sebastiao

Jose F Cascalheira

Affiliations

Soon will be listed here.

Abstract

Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3-30 μM) decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6±2.7 μM and an Emax of 31%±2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10-150 nM), an EC50 of 35±19 nM, and an Emax of 29%±5 were obtained. The combined inhibitory effect of WIN55212-2 (30 μM) 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 A1 activity, which did not modify the effect of WIN55212-2 (30 μM) on cAMP accumulation. In conclusion, the combined effect of CB1 and A1 receptors on cAMP formation is additive and CB1 receptor activity is not affected by short-term A1 receptor desensitization.

Citing Articles

Dual Influence of Endocannabinoids on Long-Term Potentiation of Synaptic Transmission.

Silva-Cruz A, Carlstrom M, Ribeiro J, Sebastiao A Front Pharmacol. 2018; 8:921.

PMID: 29311928 PMC: 5742107. DOI: 10.3389/fphar.2017.00921.

CB Receptors Mediated Inhibition of ATP-Induced [Ca]i Increase in Cultured Rat Spinal Dorsal Horn Neurons.

Long J, Lei X, Chen M, Yang S, Sun T, Zeng J Neurochem Res. 2017; 43(2):267-275.

PMID: 29127599 DOI: 10.1007/s11064-017-2414-6.

The Role of cGMP on Adenosine A 1 Receptor-mediated Inhibition of Synaptic Transmission at the Hippocampus.

Pinto I, Serpa A, Sebastiao A, Cascalheira J Front Pharmacol. 2016; 7:103.

PMID: 27148059 PMC: 4840265. DOI: 10.3389/fphar.2016.00103.

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