Effect of Acute Ethanol on Release of Endogenous Adenosine from Rat Cerebellar Synaptosomes

Abstract

The effects of pharmacologically relevant concentrations of ethanol on the release of endogenous adenosine from rat cerebellar synaptosomes were investigated. Release was conducted for 5, 10, 30, or 60 s after which time the incubation medium (containing the released adenosine) was rapidly separated from the synaptosomal membranes by vacuum filtration. The adenosine content of the filtrate was measured by HPLC–fluorescence detection. Both basal and KCl‐stimulated adenosine release consisted of an initial rapid phase, for the first 10 s, that was followed by a relatively slower phase. Basal endogenous adenosine release was estimated as 199 ± 14 pmol/mg protein/5 s. Potassium (chloride) increased adenosine release from the basal level to 433 ± 83 pmol/mg protein/5 s. Ethanol caused a dose‐dependent increase of adenosine release. The interaction between dilazep and ethanol indicates that ethanol‐stimulated release does not involve the dilazep‐sensitive transport system. The results support previous findings that indicate that cerebellar adenosine is involved in the mediation of ethanol‐induced motor disturbances in the rat.

Amethystic agents influencing toxicodynamics of ethanol

“…Считается, что острое воздействие этанолом сопровождается активацией системы аденозина [67,68]. Ключевым звеном данного феномена является повышение содержания внеклеточного аденозина.…”

“…Например, спирт в концентрации 100 мМ повышал экзоцитоз более чем в 2 раза. Высвобождение аденозина, стимулированное калием, также усиливалось в присутствии алкоголя [68];…”

Involvement of adenosinergic and dopaminergic systems in the regulation of alcohol or sucrose intake: studies in rodent models of self-administration

“…(Fredholm et al, , 2001Cauli et al, 2005; Adenosine produces hypnotic and anxiolytic effects as well as a reduction of locomotion (Deckert et al, 1998;Correa and Font, 2008), while caffeine blocks adenosine's sedative, anxiolytic and sleep-inducing effects. Ethanol increases adenosine levels by potentiating adenosine release (Clark and Dar, 1989;Fredholm and Wallman-Johansson, 1996) and by decreasing adenosine uptake (Diamond and Gordon, 1997). Secondarily, ethanol increases adenosine levels because acetate generated by ethanol metabolism promotes adenosine synthesis (Carmichael et al, 1991;Pardo et al, 2013a).…”

“…On the other hand, ethanol increases the concentration of extracellular adenosine by facilitating adenosine release (Clark and Dar, 1989), and inhibiting adenosine re-uptake (Nagy, 1990;Butler and Prendergast, 2012). Secondarily, ethanol increases adenosine levels because acetate generated by ethanol metabolism promotes adenosine synthesis (Carmichael et al, 1991;Lopez-Cruz et al, 2013;Pardo et al, 2013a).…”

“…Ethanol can increase extracellular adenosine levels by increasing adenosine release (Clark and Dar, 1989), and by decreasing adenosine uptake (Diamond and Gordon, 1994) that takes place via a facilitative nucleoside transporter (Nagy et al, 1990). …”