P2-purinoceptor-mediated autoinhibition of sympathetic transmitter release in mouse and rat vas deferens.

Effects of drugs acting at P2-purinoceptors on the release of newly taken up [3H]-noradrenaline were studied in slices of mouse and rat vas deferens. The slices were superfused and stimulated electrically, in most experiments by trains of 60 pulses/8 Hz. In mouse vas deferens, the P2-purinoceptor antagonists reactive blue 2 (1.8-100 microM) and brilliant blue G (10-300 microM) increased the stimulation-evoked overflow of tritium in a concentration-dependent manner as shown previously for suramin. Reactive blue 2, which preferentially blocks the P2Y-subtype, was the most potent compound and the compound with highest maximal effect, an increase by 104%. Pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), in contrast, caused a small increase only at a single concentration (30 microM). The effects of reactive blue 2, brilliant blue G and suramin were not additive. The P2 agonist adenosine 5'-O-(3-thio)-triphosphate (ATP gamma S) reduced the evoked overflow of tritium. As shown previously for suramin, reactive blue 2 30 microM and brilliant blue G 100 microM antagonized the effect of ATP gamma S. From the shift of the ATP gamma S concentration-response curve to the right, an apparent pKB value of 5.3 was estimated for reactive blue 2 and an apparent pKB of 4.5 for brilliant blue G. In rat vas deferens, reactive blue 2 (3-30 microM), brilliant blue G (10 microM) and suramin (30-300 microM) also increased the evoked overflow of tritium. As in the mouse, reactive blue 2 was the most potent compound and the compound with highest maximal effect, an increase by 90%.(ABSTRACT TRUNCATED AT 250 WORDS)