Inhibition by Anandamide and Synthetic Cannabimimetics of the Release of [³H]d-Aspartate and [³H]GABA from Synaptosomes Isolated from the Rat Hippocampus

Abstract

Cannabinoids (CB) can act as retrograde synaptic mediators of depolarization-induced suppression of inhibition or excitation in hippocampus. This mechanism may underlie the impairment of some cognitive processes produced by these compounds, including short-term memory formation in the hippocampus. In this study, we investigated several compounds known to interact with CB receptors, evaluating their effects on K(+)-evoked release of [3H]D-aspartate ([3H]D-ASP) and [3H]GABA from superfused synaptosomes isolated from the rat hippocampus. [3H]D-ASP and [3H]GABA release were inhibited to different degrees by the synthetic cannabinoids WIN 55,212-2; CP 55,940, and arachidonyl-2'-chloroethylamide/N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA), as well as by the endocannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2-AG). Both types of release were also inhibited by capsaicin. The inhibition produced by each of the cannabinoid compounds and capsaicin was unaffected by capsazepine or by the CB1-receptor antagonists AM-251 and SR141716A. The mechanism underlying AEA- and synthetic CB-induced inhibition of the release of [3H]GABA and [3H]D-ASP from rat hippocampal synaptosomes might not involve activation of presynaptic CB1 receptors.

ATP and purinergic receptor–dependent membrane traffic in bladder umbrella cells

“…Alternatively, the effect of anandamide and flufenamic acid could be indirect. Flufenamic acid blocks other channel types (54), while anandamide is a general inhibitor of secretion in neuronal cells and is a natural ligand for cannabinoid and TRPV1 receptors (30,31), the latter of which we previously showed to be required for ATP release by the bladder uroepithelium (55). We also observed that verapamil and dipyridamole significantly impaired ATP release, which implicates ABC and nucleoside transporters.…”

“…The general secretion inhibitor brefeldin A (BFA) dramatically reduced the release of ATP into the serosal and mucosal hemichambers ( Figure 1, A and B). Anandamide, which can block release of ATP through connexin hemichannels (8) but also acts as a ligand for cannabinoid and transient receptor potential vanilloid 1 (TRPV1) channels (30,31), markedly reduced serosal and mucosal release of ATP ( Figure 1, A and B). In contrast, flufenamic acid, which also inhibits ATP transport through connexin hemichannels (8,32), impaired mucosal but not serosal release of ATP ( Figure 1, A and B).…”

An unexpected effect of capsaicin on spontaneous GABA-ergic IPSCS in hippocampal cell cultures

“…Therefore, it cannot be ruled out that the efficacy of GABA-ergic connections made by interneurons from some other subpopulation can still be significantly modulated by capsaicin. The latter possibility is indirectly supported by the observation that the release of GABA from synaptosomes isolated from the rat hippocampus is suppressed by capsaicin [8]. The earlier described blocking of voltage-activated calcium channels in hippocampal neurons by capsaicin [9] is also in line with this hypothesis.…”

Presynaptic TRPV1 vanilloid receptor function is age- but not CB1 cannabinoid receptor-dependent in the rodent forebrain

“…Lack of TRPV 1 R-triggered release of radiolabeled neurotransmitters from synaptosomal preparations (D'Amico et al, 2004;Köfalvi et al, 2005Köfalvi et al, , 2007Cannizzaro et al, 2006;Ferreira et al, 2009) can be a result of the age of the animals used and/or of the lack of temporal resolution of the technique itself, i.e. that a fast-desensitizing capsaicin effect (Baamonde et al, 2005) is diluted in the minute-scale sampling process.…”