Evidence that transmitter release in sympathetic nerves is not set by feedback via presynaptic receptors

The possibility of negative feedback regulation of noradrenaline release was studied in the sympathetically innervated ureters of the guinea pig mounted in vitro. Tissues were transmurally stimulated with 300 pulses at 2 Hz over a range of voltages, from 10 to 60 V. It was determined that the output of transmitter increased with increasing voltage but that the effects of supposed presynaptic antagonism by yohimbine and presynaptic agonism by added noradrenaline did not fulfill the requirements of presynaptic theory governing negative feedback. It is concluded that the presynaptic effects of these drugs is neither linked to the operation of a negative feedback system nor sensitive to the perineuronal concentrations of free and active neurotransmitter.