An examination of the negative feedback function of presynaptic adrenoceptors in a vascular tissue.

1 The hypothesis was examined that presynaptic alpha-adrenoceptors exert a negative feedback function regulating noradrenergic transmission.2 Renal artery strips from cattle, pre-incubated with [(3)H]-noradrenaline, were stimulated with 300 pulses at 5 different frequencies, spanning the physiological range, and the efflux of tritium assessed both in the absence and presence of functional presynaptic receptors.3 Considerable variation in the synaptic level of free and active noradrenaline with increasing frequency was apparent from the rates of development and the magnitudes of the mechanical responses but the overflow of tritium was constant at 1, 2, 10 and 15 Hz and slightly elevated at 5 Hz, providing no evidence for presynaptic modulation of release.4 Phenoxybenzamine (3.3 x 10(-5) M) enhanced the overflow of tritium most at the lowest frequency tested and to a similar extent at the other test frequencies, except 10 Hz where its effect was slightly reduced.5 The conditions of the present experiments appeared optimal for the operation of the negative feedback system and the failure to observe an increased effectiveness of the antagonist with increasing frequency indicates that the physiological relevance of such a system is highly questionable and suggests that it may not function at all.