Adenosine-induced presynaptic inhibition of IPSCs and EPSCs in rat hypothalamic supraoptic nucleus neurones

1. The effects of adenosine on synaptic transmission in magnocellular neuro secretory cells mere investigated using whole-cell patch-clamp recordings i n acute rat hypothalamic slices that included the supraoptic nucleus. 2. Adenosine reversibly reduced the amplitude of evoked inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents in a dose-dependent manner (IC 50 approximate to 10 mu M for both types of current). 3. Depression of IPSCs and EPSCs by adenosine was reversed by the applicati on of the A(1) adenosine receptor antagonist 8-cyclopentyl-1,3-dimethylxant hine (CPT; 10 mu M) 4. When pairs of stimuli were given at short intervals, adenosine inhibitor y action was always less effective on the second of the two responses than on the first, resulting in an increased paired-pulse facilitation and sugge sting a presynaptic site of action. This observation was confirmed by analy sis of spontaneous miniature synaptic currents whose frequency, but not amp litude or kinetics, was reversibly reduced by 100 mu M adenosine. 5. CPT had no effect on synaptic responses evoked at a low frequency of sti mulation (0.05-0.5 Hz), indicating the absence of tonic activation of A(1) receptors under these recording conditions. However, CPT inhibited a time-d ependent depression of both IPSCs and EPSCs induced during a 1 Hz train of stimuli. 6. Taken together, these results suggest that adenosine can be released wit hin the supraoptic nucleus at a concentration sufficient to inhibit the rel ease of GABA and glutamate via the activation of presynaptic A(1) receptors . By its inhibitory feedback action on the major afferent inputs to oxytoci n and vasopressin neurones, adenosine could optimally adjust electrical and secretory activities of hypothalamic magnocellular neurones.