Autoinhibition, sympathetic cotransmission and biphasic contractile responses to trains of nerve stimulation in the rodent vas deferens.

1. The present review critically discusses the evidence for and against the various hypotheses that have been proposed to explain the biphasic contractile response of the rodent vas deferens to trains of electrical field stimulation (EFS). 2. It is widely accepted that the initial component of the biphasic response of the rodent isolated vas deferens to trains of EFS is mediated by ATP and the second slower tonic contractions is mediated by noradrenaline (NA). This theory is based on the ability of antagonists of the post-junctional receptors for these neurotransmitters to inhibit the respective components of the biphasic response and on the ability of exogenous application of either ATP or NA to mimic the responses of each phase. 3. Prejunctional autoinhibition has also been proposed as the cause of the biphasic response. This is based primarily on the ability of alpha 2-adrenoceptor antagonists to transform responses from biphasic to monophasic and on the ability of neuronal NA uptake inhibitors to accentuate the separation of the two phases. 4. Atypical or extrajunctional NA receptors have also been proposed to be the mediators of the component of the response to nerve stimulation that is resistant to the traditional alpha-adrenoceptor antagonists. 5. Different contractile mechanisms and/or sources of calcium have also been postulated to cause the biphasic response. Blockers of intracellular Ca2+ mobilization are able to block the initial component, while blockers of extracellular Ca2+ entry inhibit the second tonic phase. 6. It is concluded that because alpha 1-adrenoceptor antagonists and blockers of P2 purinoceptors have also been shown to block both phases of the response to trains of EFS, prejunctional auto-inhibitory mechanisms perhaps provide the most sound explanation for the phenomenon of the biphasic contractile response to trains of EFS.