Autonomic Neurotransmission

Introduction

• Neurohumoral transmission — the carriage of a nerve impulse across a synapse or neuroeffector junction by release of a specific chemical messenger (neurotransmitter) rather than electrically; it is the conceptual basis of all autonomic pharmacology, since every step is a potential drug target.
• Autonomic outflow — two efferent divisions — sympathetic (thoracolumbar, T1–L2/L3) and parasympathetic (craniosacral; CN III, VII, IX, X and S2–S4) — plus the semi-autonomous enteric nervous system (>150 million neurons; myenteric/Auerbach and submucosal/Meissner plexuses).
• Transmitter map — ACh at all preganglionic fibres, all postganglionic parasympathetic fibres, sympathetic-cholinergic fibres to sweat glands, the somatic NMJ and the adrenal medulla; noradrenaline (NE) at most postganglionic sympathetic fibres; some parasympathetic fibres are nitrergic (NO).
• Adrenal medulla — a modified sympathetic ganglion — preganglionic cholinergic (N_N) input releases EPI ≈80% and NE ≈20% directly into the blood.
• Historical landmarks — Elliott (1905) sympathetic-EPI hypothesis; Dale (1914) muscarinic vs nicotinic ACh actions; Loewi (1921) two-frog-heart proof of "Vagusstoff" (ACh); von Euler (1946) identified NE as the sympathetic transmitter.