CAFFEINE ENHANCES SYMPATHETIC PURINERGIC AND NORADRENERGIC TRANSMISSION IN THE GUINEA-PIG ISOLATED VAS-DEFERENS

Intracellular recording techniques were used to monitor the resting me mbrane potential of smooth muscle cells and the excitatory junction po tentials (EJPs) evoked by stimulation of the hypogastric nerve. Stimul ation with trains of 15 pulses at 1 Hz or 0.33 Hz evoked individual EJ Ps which increased in amplitude from the first pulse and reached a pla teau after 6-8 pulses. Stimulation at 1 Hz resulted in EJPs facilitati ng to a plateau level of approximately 25 mV, whereas with stimulation at 0.33 Hz the EJPs only facilitated to a plateau level of about 12 m V. With stimulation at 1 Hz, caffeine (3 mM and 10 mM), increased the amplitude of the first few EJPs in each train and decreased the extent of facilitation and reduced the amplitude of fully facilitated EJPs. In comparison, the amplitude of all EJPs evoked by stimulation at 0.33 Hz was increased by caffeine (3 mM and 10 mM). With 0.33 Hz stimulati on, facilitation of the first few EJPs was observed in the presence of 3 mM caffeine but not in the presence of 10 mM caffeine. In the prese nce of the alpha(2)-adrenoceptor antagonist idazoxan, caffeine (3 mM a nd 10 mM) still enhanced the amplitude of EJPs early in trains of stim ulation but there was no depression of EJPs later in the trains. Simil arly, in reserpine-treated vasa deferentia, caffeine (3 mM) enhanced E JPs early in the train of stimulation at 1 Hz and there was no depress ion of EJPs at the end of the train. In addition to electrophysiologic al experiments, the effect of caffeine (0.1-30 mM) on the resting and stimulation-induced (S-I) efflux of radioactivity was investigated in guinea-pig isolated vasa deferentia previously incubated with [H-3]-no radrenaline. Caffeine (10 mM) did not affect the resting efflux of [H- 3]-noradrenaline but significantly enhanced the S-I efflux by 150-160% . The present findings suggest that caffeine enhances sympathetic puri nergic and noradrenergic transmission at the sympathetic neuroeffector junction in the guineapig vas deferens. Moreover, the increased relea se of transmitter noradrenaline can modulate purinergic transmission b y activation of alpha(2)-adrenoceptors located at sympathetic neuroeff ector sites.