Abstract
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 μM) and brilliant blue G (10–300 μM) 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%. Pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), in contrast, caused a small increase only at a single concentration (30 μM). The effects of reactive blue 2, brilliant blue G and suramin were not additive. The P2 agonist adenosine 5′-O-(3-thio)-triphosphate (ATPγS) reduced the evoked overflow of tritium. As shown previously for suramin, reactive blue 2 30 μM and brilliant blue G 100 μM antagonized the effect of ATPγS. From the shift of the ATPγS 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 μM), brilliant blue G (10 μM) and suramin (30–300 μM) 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 9001o. As previously demonstrated in the mouse, suramin (300 μM) increased the evoked overflow of tritium only when rat vas deferens slices were stimulated by trains of 60 pulses at 1 or 8 Hz, but not when they were stimulated by trains of 6 pulses/100 Hz.
The results confirm the operation of a P2-purinoceptor-mediated prejunctional negative feedback controlling the release of noradrenaline in mouse vas deferens and demonstrate the same mechanism in rat vas deferens. The prejunctional P2-purinoceptors are P2Y-like in both species. They are a novel kind of autoreceptors, operating in parallel to prejunctional α2-autoreceptors.
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Correspondence to: I. von Kügelgen at the above address
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von Kügelgen, I., Kurz, K. & Starke, K. P2-purinoceptor-mediated autoinhibition of sympathetic transmitter release in mouse and rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 349, 125–132 (1994). https://doi.org/10.1007/BF00169828
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DOI: https://doi.org/10.1007/BF00169828