Rate limiting factors in sympathetic neurotransmitter secretion

Isolated superfused field stimulated preparations of guinea-pig vas deferens, in which the neural stores of noradrenaline (NA) had been labelled by preincubation with tritium-marked (-)-NA, were used to study the factors regulating the amount of NA secreted from the nerves, per applied shock. The results indicate that "Stimulation secretion coupling" in this tissue is subject to 2 different kinds of facilitation, one independent and one dependent on nerve stimulation frequency. Kinetic analysis of the calcium dependence of transmitter secretion, after removal of alpha-adrenoceptor mediated negative feedback control, suggests that there is a definite upper limit to the amount of transmitter which can be secreted, per pulse, from each "secretary area" of the nerves. The low Q(10) value of this apparent V(maz) suggests that the rate limiting factor is non-enzymatic in nature. It is proposed that the ultimately rate limiting factor in NA secretion may rather be the number of vesicles in each potential "secretary area" which are in a suitable position within the nerve for active participation in the secretion of transmitter.