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Chapter 6: Mind the Gap: Chemical Transmission from Sympathetic Nerves to Organs

Everything of importance has been said before by somebody who did not discover it.

Alfred North Whitehead

When compared injections of adrenaline, activation of sympathetic nerves has many similar actions on organs throughout the body. The dazzling explanation for their comparable effects emerged only after much hard work. The solution had broad implications for understanding the inner workings of the nervous system and for the invention of powerful drugs. Solving how the companion parasympathetic nerves activated target organs posed an analogous challenge. The resolution of both questions involved the astonishing demonstration that sympathetic and parasympathetic nerve endings release chemicals called neurotransmitters that move across the narrow gap from nerve endings to cells in target organs. Since the stories leading to the identification of these neurotransmitters are intertwined in concept, time, place, and people, they will be discussed together. These accounts emphasize the lives and contributions of very prominent scientists involved in this research, especially Henry Dale, Otto Loewi, US von Euler, and Julius Axelrod.

The Concept of Chemical Neurotransmission

John Langley (1852–1925) made great progress in understanding the physiology of the autonomic nervous system over a 50-year career at Cambridge University in England. He divided the autonomic nervous system into two components termed the sympathetic and the parasympathetic nervous systems. The sympathetic nerves emerge from the spinal cord largely in the chest (thoracic) whereas the parasympathetic nerves originate either in the brainstem in the head (cranial nerves) or in the low back (sacral region). In many cases, the effects of the sympathetic and parasympathetic nervous systems oppose each other in regulating organ function. An advantage of opposing systems is that in urgent situations, needed changes in organ function can be implemented very quickly; for example, in the case of a requirement for a rapid increase in heart rate, the accelerator of heart beat (sympathetic nerve) can be pushed harder as the decelerator of the rate (parasympathetic nerve) is simultaneously turned off.

Langley developed a schematic representation of the autonomic nervous system that described two key neurons. The first neuron—named the preganglionic neuron—is heavily regulated by signals from the brain. The preganglionic neuron sends signals that are received by postganglionic neuron in structures called ganglions; the postganglionic neurons then relay the signals from the ganglion to target organs. The brain uses the autonomic nervous system to regulate many functions that are outside of conscious control.

In 1899, Max Lewandowski (1876–1918) demonstrated that responses in the eyes were very similar when he compared intravenous injections of adrenal extracts with stimulating the sympathetic nerves going to the eye. In 1901, Langley confirmed and extended Lewandowski’s results; Langley demonstrated that the effects of adrenal extracts persisted even after the sympathetic nerves to the eye had been destroyed, strongly suggesting that the active substance in the extracts acted directly on the eyes.