Neural ATP release and its alpha 2-adrenoceptor-mediated modulation in guinea-pig vas deferens

Abstract

Contractions, release of previously stored [3H]-noradrenaline (measured as overflow of total tritiated compounds) and release of ATP elicited by electrical field stimulation (210 pulses, 7 Hz) were studied in the superfused vas deferens of the guinea pig. Prazosin and suramin were used to suppress non-neural ATP release, and effects of bromoxidine and rauwolscine on the neural release thus isolated were examined. Electrical stimulation elicited reproducible contraction, tritium overflow and ATP overflow. Both prazosin (0.03-3 microM) and suramin (30-300 microM) reduced contractions as well as the evoked overflow of ATP. No visible contraction remained in 21 of 28 tissues exposed to prazosin 0.3 microM combined with suramin 300 microM. The evoked overflow of ATP under these conditions was about 17% of that observed in the absence of drugs. In the presence of prazosin 0.3 microM and suramin 300 microM, bromoxidine (0.01-1 microM) decreased and rauwolscine (0.1-10 microM) increased the evoked overflow of both tritium and ATP. Rauwolscine increased the evoked overflow of tritium to a significantly greater extent than the overflow of ATP. It is concluded that the overflow of ATP elicited by electrical (neural) stimulation in the presence of prazosin 0.3 microM and suramin 300 microM reflects purely neural release of ATP. This release of ATP, like the release of noradrenaline, is modulated through prejunctional alpha 2-adrenoceptors. The alpha 2-adrenoceptor modulation of the release of noradrenaline seems to be more marked than the modulation of the release of ATP.