Autonomic nervous system concepts

The concept of chemical neurotransmission originated in the 1920s with the classic experiments of Otto Loewi (which were themselves inspired by a dream), who demonstrated that by transferring the ventricular fluid of a stimulated frog heart onto an unstimulated frog heart he could reproduce the effects of a (parasympathetic) nerve stimulus on the unstimulated heart (Loewi Navratil, 1926). Subsequently, it was found that acetylcholine was the neurotransmitter released from these parasympathetic nerve fibers. As well as playing a critical role in synaptic transmission in the autonomic nervous system and at vertebrate neuromuscular junctions (Dale, 1935), acetylcholine plays a central role in the control of wakefulness and REM sleep. Some have even gone as far as to call acetylcholine a neurotransmitter correlate of consciousness (Perry et al., 1999). 

The concept of chemical transmission in the nervous system arose in the early years of the century when it was discovered that the functioning of the autonomic nervous system was largely dependent on the secretion of acetylcholine and noradrenaline from the parasympathetic and sympathetic nerves respectively. The physiologist Sherrington proposed that nerve cells communicated with one another, and with any other type of adjacent cell, by liberating the neurotransmitter into the space, or synapse, in the immediate vicinity of the nerve ending. He believed that transmission across the synaptic cleft was unidirectional and, unlike conduction down the nerve fibre, was delayed by some milliseconds because of the time it took the transmitter to diffuse across the synapse and activate a specific neurotransmitter receptor on the cell membrane. 

Studies of neuromuscular junctions of the autonomic nervous system as early as 1904 led to the suggestion that adrenaline might be released at the nerve endings. Later it was shown that, while adrenaline does serve as a transmitter at neuromuscular junctions in amphibians, it is primarily a hormone in mammals. Nevertheless, it was through this proposal that the concept of chemical communication in synapses was formulated. By 1921, it was shown that acetylcholine is released at nerve endings of the parasympathetic system, and it later became clear the motor nerve endings of the somatic system also release acetylcholine. 

The definition of receptors as specific sites for drug action owes much to the work of John Newton Langley [ 1852-1925 ] and Paul Ehrlich [ 1854-1915 ]. Their separate work on the autonomic nervous system and toxins and chemotherapeutic agents led to the concept of a receptor that possesses both recognition and transduction components and of chemotherapeutic molecules possessing discrete molecular features subserving specific functions ... 

Appenzeller O, Oribe E The Autonomic Nervous System An Introduction to Basic and Clinical Concepts. Elsevier Science, Amsterdam, The Netherlands (1997). 

Loewi s work was confined to the autonomic nervous system. Kibjakow (63) and later Dale and his associates tried to extend this concept and suggested that acetylcholine might be the transmitter across ganglionic synapses and at neuromuscular junctions. Their evidence was based essentially on the same type of experiments as was applied in the case of the peripheral autonomic system liberation of acetylcholine after stimulation of preganglionic fibers or motor nerves, stimulation of the sympathetic ganglion and the striated muscle by injection ofij small amounts of ACh, and potentiation of the effects of nerve stimulation by eserinization. The results have been reviewed by Brown (16). 

The APUD concept of a diffuse neuroendocrine system has been defined as follows by A.G.E.Pearse [in Centrally Acting Peptides, J. Hughes (ed.), MacMillan, 1978] The cells of the APUD series, producing peptides active as hormones or as neurotransmitters, are all derived from neuroendocrine-programed cells originating from the ectoblast. They constitute a third (endocrine or neuroendocrine) division of the nervous system whose cells act as third line effectors to support, modulate or amplify the action of neurons in the somatic and autonomic divisions, and possibly as tropins to both neuronal and non-neuronal cells . 

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