Patterns of peptide discharge — implications for Dale’s principle

Summary

According to Dale’s principle, a neuron uses the same transmitter(s) at all its branches, reflecting its metabolic unity. However, there are reasons to doubt the universal validity of this hypothesis. Peptide secretion involves a fundamentally different metabolic pathway from that followed by classical transmitters. Furthermore, peptides are stored in secretory granules and released by exocytosis from mainly nonsynaptic regions of the plasmalemma, whereas transmitters are typically discharged at specialised synaptic thickenings. Thus different regions of the neuronal surface are responsible for the discharge of different classes of chemical mediators — a finding quite at variance with Dale’s principle. The principle retains valuable predictive powers if transmitters and peptides are considered in isolation from each other, although it will not be vindicated invariably even on this basis.