Caffeine enhances sympathetic purinergic and noradrenergic transmission in the guinea-pig isolated vas deferens.
Intracellular recording techniques were used to monitor the resting membrane potential of smooth muscle cells and the excitatory junction potentials (EJPs) evoked by stimulation of the hypogastric nerve. Stimulation with trains of 15 pulses at 1 Hz or 0.33 Hz evoked individual EJPs which increased in amplitude from the first pulse and reached a plateau after 6-8 pulses. Stimulation at 1 Hz resulted in EJPs facilitating 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 mV. 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 stimulation, 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 presence of the alpha 2-adrenoceptor antagonist idazoxan, caffeine (3 mM and 10 mM) still enhanced the amplitude of EJPs early in trains of stimulation but there was no depression of EJPs later in the trains. Similarly, in reserpine-treated vasa deferentia, caffeine (3 mM) enhanced EJPs early in the train of stimulation at 1 Hz and there was no depression of EJPs at the end of the train. In addition to electrophysiological 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 [3H]-noradrenaline. Caffeine (10 mM) did not affect the resting efflux of [3H]-noradrenaline but significantly enhanced the S-I efflux by 150-160%. The present findings suggest that caffeine enhances sympathetic purinergic and noradrenergic transmission at the sympathetic neuroeffector junction in the guinea-pig vas deferens. Moreover, the increased release of transmitter noradrenaline can modulate purinergic transmission by activation of alpha 2-adrenoceptors located at sympathetic neuroeffector sites.
Ziogas
J
J
Department of Pharmacology, University of Melbourne, Parkville Victoria, Australia.
O'Farrell
M
M
Slaughter
M
M
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D014316:Tritium; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation / Q000502:physiology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D011983:Receptors, Purinergic; D014316:Tritium; D002110:Caffeine; D012110:Reserpine; D009638:Norepinephrine; D019329:Idazoxan