Autonomic nerve endings, effects

Both the G- and V-agents have the same physiological action on humans. They are potent inhibitors of the enzyme acetylcholinesterase (AChE), which is required for the function of many nerves and muscles in nearly every multicellular animal. Normally, AChE prevents the accumulation of acetylcholine after its release in the nervous system. Acetylcholine plays a vital role in stimulating voluntary muscles and nerve endings of the autonomic nervous system and many structures within the CNS. Thus, nerve agents that are cholinesterase inhibitors permit acetylcholine to accumulate at those sites, mimicking the effects of a massive release of acetylcholine. The major effects will be on skeletal muscles, parasympathetic end organs, and the CNS. 

The anatomy of autonomic synapses and junctions determines the localization of transmitter effects around nerve endings. Classic synapses such as the mammalian neuromuscular junction and most neuron-neuron synapses are relatively "tight" in that the nerve terminates in small boutons very close to the tissue innervated, so that the diffusion path from nerve terminal to postsynaptic receptors is very short. The effects are thus relatively rapid and localized. In contrast, junctions between autonomic neuron terminals and effector cells (smooth muscle, cardiac muscle, glands) differ from classic synapses in that transmitter is released from a chain of varicosities in the postganglionic nerve fiber in the region of the smooth muscle cells rather than boutons, and autonomic junctional clefts are wider than somatic synaptic clefts. Effects are thus slower in onset and often involve many effector cells. 

The prostaglandins and thromboxanes have major effects on four types of smooth muscle airway, gastrointestinal, reproductive, and vascular. Other important targets include platelets and monocytes, kidneys, the central nervous system, autonomic presynaptic nerve terminals, sensory nerve endings, endocrine organs, adipose tissue, and the eye (the effects on the eye may involve smooth muscle). 

Usually excitatory, except for some parasympathetic nerve endings where it is inhibitory (such as the effect on the heart by the vagus nerve). Secreted by many neurons, including those in the motor area of the brain, basal ganglia, skeletal muscle motor neurons, all preganglionic autonomic nervous system neurons, all postganglionic parasympathetic neurons, and some postganglionic sympathetic neurons. 

Amine uptake blockade The drugs that block norepinephrine transporters in the CNS (eg, tricyclics) also inhibit the reuptake of norepinephrine at nerve endings in the autonomic nervous system. Likewise, MAO inhibitors increase NE in sympathetic nerve terminals. In both cases, this can lead to peripheral autonomic sympathomimetic effects. However, longterm use of MAOIs can decrease blood pressure. 

This type of analysis demonstrates the predominant effect of cholinesterase inhibition by these compounds in the autonomic nervous system of the dog to be manifest at post-ganglionic parasympathetic nerve-endings. 

The finding that AChE is located in synapses on both presynaptic and postsynaptic membranes, and in some cases only on the presynaptic membrane, is not clearly understood. In the synapses of skeletal muscles, where a very rapid hydrolysis of ACh is needed for the transmission of high-frequency impulses, AChE is located chiefly postsynaptically. Probably the location of AChE in immediate proximity to ChR fadlitates the speediest hydrolysis of ACh. In autonomic ganglia, where AChE is located only presynaptically, the simple diffusion of ACh from the synaptic cleft may play a rdle in stopping its effect It seems probable that in ganglia the presynaptic AChE can hydrolyse ACh only after its interaction with the receptors of the postsynaptic membrane. When released by the nerve ending, ACh s concentration near the presynaptic membrane is so high that a substrate inhibition of AChE must occur, which enables ACh to reach the postsynaptic membrane without considerable loss. 

Introduction - Although 46 years have elapsed since the relatively simple experiments of Otto Loewi demonstrated neurohumoral transmission at autonomic junctions, it is only during the past 10 years that this theory of neurotransmission has become almost universally accepted. Indeed, more evidence favoring the extension of this theory to nerve-nerve junctions (synapses) in the central nervous system (CNS) has been presented in the past 7 years than in the entire preceding quarter-century. Briefly stated, the theory of neurohumoral transmission holds that nerves produce their physiologic effects by releasing chemical substances which act on the cell that the nerve endings innervate, rather than by the continuous flow of bio-electric currents. ... 

Most of the direct organ system effects of muscarinic cholinoceptor stimulants are readily predicted from a knowledge of the effects of parasympathetic nerve stimulation (see Table 6-3) and the distribution of muscarinic receptors. Effects of a typical agent such as acetylcholine are listed in Table 7-3. The effects of nicotinic agonists are similarly predictable from a knowledge of the physiology of the autonomic ganglia and skeletal muscle motor end plate. 

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