Conditions required for the inhibitory feedback loop in noradrenergic transmission

Abstract

One of the most striking advances in the study of neurotransmission during the past decade has been the recognition that nerve terminals have receptor sites which, when activated, modulate transmitter release^1–4. The most extensively studied have been the α-adrenoceptors of noradrenergic sympathetic terminals, activation of which inhibits transmitter release. It is widely believed that the prejunctional α-adrenoceptors are activated by transmitter noradrenaline, which results in inhibition of subsequent transmitter release^1–6, thereby forming an inhibitory feedback system. However, this hypothesis has recently been challenged by Angus and Korner⁷ on the basis of observations made with short trains of stimulation applied to the intramural sympathetic nerves of isolated guinea pig atria. We have, therefore, re-examined the question using the same tissue and applying not only short, but also longer, trains of stimulation. We report here a time delay before the inhibitory feedback effect through prejunctional α-adrenoceptors is manifested; thus the effect will not be observed unless a sufficiently long train of stimulation is applied. Furthermore, there is no pulse-to-pulse inhibitory feedback regulation of transmitter release for trains of stimulation in which the pulse interval is extended to 8 s.