Neuroeffector junction

Sympathetic nervous system. That portion of the autonomic nervous system that utilizes norepinephrine as a neurotransmitter at its neuroeffector junctions. 

Neurohumoral transmitters are chemicals that facilitate the transmission of nerve impulses across nerve synapses and neuroeffector junctions. Acetylcholine is a neurohumoral transmitter that is present in the peripheral autonomic nervous system, in the somatic motor nervous system, and in some portions of the central nervous system. 

Describe how the neuroeffector junction in the autonomic nervous system differs from that of a neuron-to-neuron synapse... 

Synapses between the autonomic postganglionic neuron and effector tissue — the neuroeffector junction — differ greatly from the neuron-to-neuron synapses discussed previously in Chapter 5 (see Table 9.1). The postganglionic fibers in the ANS do not terminate in a single swelling like the synaptic knob, nor do they synapse directly with the cells of a tissue. Instead, the axon terminals branch and contain multiple swellings called varicosities that lie across the surface of the tissue. When the neuron is stimulated, these varicosities release neurotransmitter over a large surface area of the effector tissue. This diffuse release of the neurotransmitter affects many tissue cells simultaneously. Furthermore, cardiac muscle and most smooth muscle have gap junctions between cells. These specialized intercellular communications... 

For any substance to serve effectively as a neurotransmitter, it must be rapidly removed or inactivated from the synapse or, in this case, the neuroeffector junction. This is necessary in order to allow new signals to get through and influence effector tissue function. Neurotransmitter activity may be terminated by three mechanisms ... 

The primary mechanism used by cholinergic synapses is enzymatic degradation. Acetylcholinesterase hydrolyzes acetylcholine to its components choline and acetate it is one of the fastest acting enzymes in the body and acetylcholine removal occurs in less than 1 msec. The most important mechanism for removal of norepinephrine from the neuroeffector junction is the reuptake of this neurotransmitter into the sympathetic neuron that released it. Norepinephrine may then be metabolized intraneuronally by monoamine oxidase (MAO). The circulating catecholamines — epinephrine and norepinephrine — are inactivated by catechol-O-methyltransferase (COMT) in the liver. 

Compared to a,-receptors, a2-receptors have only moderate distribution on the effector tissues however, they have important presynaptic effects. Alpha-one receptors are found on effector tissue cells at the neuroeffector junction the a2-receptors are found on the varicosities of the postganglionic neuron. Norepinephrine released from this neuron not only binds to the a.j-receptors on the effector tissue to cause some physiological effect but also binds to the a2-receptors on the neuron. Alpha-two receptor stimulation results in presynaptic inhibition" or in a decrease in the release of norepinephrine. In this way, norepinephrine inhibits its own release from the sympathetic postganglionic neuron and controls its own activity. Both ar and a2-receptors have equal affinity for norepinephrine released directly from sympathetic neurons as well as circulating epinephrine released from the adrenal medulla. 

Acetylcholine (ACh) The first neurotransmitter to be discovered. It is located at numerous synapses and neuroeffector junctions, in both the central and peripheral nervous systems. 

Acetylcholinesterase The catabolic enzyme that rapidly terminates the physiological action of acetylcholine at synapses and neuroeffector junctions. 

The N-methyl carbamate esters cause reversible carbamylation of the acetylcholinesterase enzyme, allowing accumulation of acetylcholine, the neuromediator substance, at parasympathetic neuroeffector junctions (muscarinic effects), at... 

Indirect sympathomimetics (B) are agents that elevate the concentration of NE at neuroeffector junctions, because they either inhibit re-uptake (cocaine), facilitate release, or slow breakdown by MAO, or exert all three of these effects amphetamine, metham-phetamine). The effectiveness of such indirect sympathomimetics diminishes or disappears (tachyphylaxis) when ve-Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Presynaptic a2-adrenoceptors function like sensors that enable norepinephrine concentration outside the axolemma to be monitored, thus regulating its release via a local feedback mechanism. When presynaptic a2-re-ceptors are stimulated, further release of norepinephrine is inhibited. Conversely, their blockade leads to uncontrolled release of norepinephrine with an overt enhancement of sympathetic effects at Pi-adrenoceptor-mediated myocardial neuroeffector junctions, resulting in tachycardia and tachyarrhythmia. 

So, parasympathetic nerves use acetylcholine as a neurotransmitter and cholinomimetic drugs mimic the action of acetylcholine at its receptors. Muscarinic receptor subtypes are found on neuroeffector junctions. Nicotinic receptor subtypes are found on ganglionic synapses. Chohnomimetics can be classified as ... 

There are two major types of cholinesterases acetylcholinesterase (AChE) and pseudocholinesterase (pseudo-ChE). AChE (also known as true, specific, or erythrocyte cholinesterase) is found at a number of sites in the body, the most important being the cholinergic neuroeffector junction. Here it is localized to the prejunctional and postjunctional membranes, where it rapidly terminates the action of synaptically released ACh. It is essential to recognize that the action of ACh is ter-... 

Transmission through autonomic ganglia is more complex than neurotransmission at the neuromuscular and postganglionic neuroeffector junctions and is subject to numerous pharmacological and physiological influences. In some ganglionic synapses, especially at parasympathetic ganglia, there is a simple presynaptic to postsynaptic cell relationship in others, the presynaptic to postsynaptic cell relationship may involve neurons interposed between the presynaptic and postsynaptic elements (interneurons). 

Unlike the receptors at postganglionic neuroeffector junctions or at skeletal neuromuscular junctions, both types of cholinergic receptors, that is, nicotinic and mus-... 

Predominant Autonomic Tone at Various Neuroeffector Junctions and the Effect Produced by Gangiionic Biockade... 

Vecuronium bromide (Norcuron) is chemically identical to pancuronium except for a tertiary amine in place of a quaternary nitrogen. However, some of the drug will exist as the bisquatemary compound, depending on body pH. Vecuronium has a moderate onset of action (2.4 minutes) and a duration of effect of about 50 minutes. Like pancuronium, it does not block ganglia or vagal neuroeffector junctions, does not release histamine, and is eliminated by urinary excretion. 

The chemical transmitters may be small molecules— notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively. Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the endogenous opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland). 

Burnstock G Non-synaptic transmission at autonomic neuroeffector junctions. Neurochem Int 2008 52 14. [ 17493707]... 

Carbamates effect the reversible carbamylation of acetylcholinesterase, permitting accumulation of acetylcholine at cholinergic neuroeffector junctions (muscarinic effects), at the myoneural junctions of skeletal muscle, and in the autonomic ganglia (nicotinic effects). CNS function is also impaired. However the relatively large dissociation constant of the carbamyl-enzyme complex indicates that it dissociates more readily than does the organophosphate-enzyme complex, mitigating the toxicity of the carbamate pesticides. The reversibility of the carbamyl-enzyme complex affects (limits) the utility of blood enzyme measurements as a diagnostic tool. 

Excitation of the parasympathetic division causes release of acetylcholine at neuroeffector junctions in different target organs. The major effects are summarized in (A) (blue arrows). Some of these effects have therapeutic applications, as indicated by the clinical uses of parasympathomimetics (P-106). 

Sarin was involved in terrorist attacks in Japan (Okumura et al, 2003 Okudera, 2002). The increase in sympathetic and parasympathetic tone results in tachycardia, ST-segment modulation (Abraham et al, 2001), and arrhythmia. Inhibition of cholinesterase within the neuroeffector junction also affects nerve impulse transmission by direct action. Direct action on muscarinic or nicotinic ACh receptors (Somani et al, 1992) is observed when the blood level of sarin exceeds the micromolar level. Sarin inhibits RBC-AChE 80-100% as well as plasma-BChE between 30 and 50% (Grob and Harvey, 1958). It also binds to aliesterase, an enzyme that contributes to ester-link hydrolysis. 

What types of molecules act as neurotransmitters and how does the process of neurotransmission proceed Following the identification of acetylcholine (ACh) as a chemical neurotransmitter by Leowi, noradrenaline (or norepinephrine, NE) was identified through the work of Dale, Cannon and others as the neurotransmitter at many sympathetic neuroeffector junctions. Although ACh and NE are quite different from each other from the chemical point of view, they do share certain key features in terms of the way they act as neurotransmitters. These features are also shared by numerous other substances... 

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