Catecholaminergic neurotransmission: flagship of all neurobiology

The paper describes, with focus on the first half of the century, the roles played by study of the sympathoadrenal system for developing modern neurobiology. Adrenaline isolated from extracts of adrenal medulla was the first intercellular messenger to be chemically identified and synthesized. Similarities between effects of adrenaline and sympathetic nerve stimulation led to the first concrete proposal of chemical neurotransmission. That effluent from a sympathetically or parasympathetically stimulated frog heart induced acceleration or slowing of an unstimulated recipient heart was the first conclusive proof of chemical neurotransmission. Acetylcholine (in parasympathetic or somatomotor) and noradrenaline (in sympathetic nerves) are the first identified mammalian neurotransmitters. The existence of a'receptive substance for adrenaline' represents the first proposal that target cells recognize and react to the released transmitter. Deviations for the '-ergic concept, in which sympathetic and parasympathetic nerves are termed 'adrenergic' and 'cholinergic', led to discovery of 'non-adrenergic, non-cholinergic' nerves and a range of other transmitters. That some effects of e.g. sympathetic nerve stimulation are not blocked by any noradrenaline antagonist led to the recognition that some nerves utilize more than one transmitter. Noradrenaline in sympathetic nerves was the first neurotransmitter to be visualized in the light microscope. catecholamines in adrenal medulla and sympathetic nerves were the first messengers to be shown to be stored in vesicles.