A comparison of the effects of exogenous and endogenous prostaglandins on fast and slow contractions of field-stimulated guinea-pig vas deferens

Abstract

1. This study has compared the effects of exogenous and endogenous prostaglandins on the two phases of contraction of the guinea-pig vas deferens produced by electrical field stimulation. Prostaglandin E2 (PGE2), sulprostone and arachidonic acid dose-dependently and completely inhibited the first (fast) phase of contraction, with IC50s of 2.6 nM, 0.65 nM and 2.2 microM, respectively. 2. Following desensitization of the receptor for adenosine triphosphate (ATP) with alpha, beta-methylene ATP, PGE2, sulprostone and arachidonic acid dose-dependently inhibited the second (slow) phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation, but the inhibition was incomplete (up to only 30%). Indomethacin (2.8 microM) reduced the effect of arachidonic acid. On its own, indomethacin (0.3 to 6.0 microM) had no consistent effect although, on some tissues, a slight potentiation of the contractions was seen. 3. Cicaprost (a PGI2 analogue) at low concentrations (0.5 to 30 nM) potentiated the first phase of contraction but even at high concentrations, had no consistent effect on the second phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation. 4. PGE2, sulprostone and cicaprost potentiated contractions of the guinea-pig vas deferens produced by exogenous ATP. PGE2 and sulprostone also potentiated contractions produced by exogenous noradrenaline, whereas cicaprost had no consistent effect on the response to noradrenaline. 5. These findings indicate that prostaglandins of the E-series inhibit the second phase of contraction as well as the first phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation. However, the extent of the inhibition is much less for the second phase than for the first phase. The reasons for this differential action of PGE are not clear. 6. Cicaprost potentiates the first phase but not the second phase of contraction. Since cicaprost potentiates the contractions produced by exogenous ATP, but not by exogenous noradrenaline, by an action presumably on post-junctional IP receptors, the potentiating action of cicaprost on the first phase of contraction produced by electrical field stimulation would appear to be satisfactorily explained through the action of cicaprost on these post-junctional IP receptors. 7. Exogenous arachidonic acid is apparently converted predominantly to PGE2 by the vas deferens, since the action of arachidonic acid mimicked that of PGE2 and was reduced by indomethacin. However, there was little evidence that sufficient PGE2 is generated during a short period (15 s) of sympathetic nerve stimulation for it to have any significant inhibitory effect on the size of the contractions produced.