Feedback inhibition of responses of rat vas deferens to twin pulse stimulation

Application of a pair of identical pulses of field stimulation to the rat isolated vas deferens results in two responses, the second of which is always smaller than the first, the reduction being inversely related to the interval between the pulses. This effect is due, in part, to the negative feedback inhibition of noradrenaline release, an event which has been demonstrated in a variety of noradrenergically innervated tissues. The ratio of the second response to the first response (the B/A ratio), is increased by substances with antagonistic activity at prejunctional a₂-receptors, and decreased by inhibitors of the neuronal uptake process. The procedure allows an estimate of the relative activity of antagonists at prejunctional a-receptors.