Nicotine Ganglionic Transmission

Although nicotine mimics the action of ACh at the receptors, it cannot duplicate the time course of intrasynap-tic agonist concentration required for appropriate high-frequency gangUonic activation. The concentration of nicotine in the synaptic cleft can neither build up as rapidly as that of ACh released from nerve terminals nor can nicotine be eUminated from the synaptic cleft as quickly as ACh. 

The ganglionic effects of ACh can be blocked by tetraethylammonium, hexa-methonium, and other substances (ganglionic blockers). None of these has intrinsic activity, that is, they fail to stimulate ganglia even at low concentration some of them (e.g hexamethonium) actually block the cholinoceptor-linked ion channel, but others (mecamyla-mine, trimethaphan) are typical receptor antagonists. 

First neuron Preganglionic Second neuron postganglionic 

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Atropine, an alkaloid from Atropa belladonna, is the classical parasympatholytic compound. It competes with acetylcholine for the binding at the muscarinic receptor. Its affinity towards nicotinic receptors is very low, so that it does not interfere with the ganglionic transmission or the neuromotor transmission, at least in therapeutic dosages. However, in the central nervous system muscarinic receptor do play an important role and while atropine can penetrate the blood-brain barrier it exerts pronounced central effects. Atropine, like all other antagonists of the muscarinic acetylcholine receptor inhibit the stimulatory influence of the parasympathetic branch of the autonomous nervous system. All excretory glands (tear, sweat, salivary, gasto-intestinal, bronchi) are... 

Neurotransmission at both cholinergic and adrenergic synapses can be influenced by a variety of naturally occurring and synthetic drugs (Table 38.2). For example, ACh secretion is drastically reduced in the presence of botulinum toxin which contains proteases that cleave proteins vital to the process of exocytosis. Nicotine, one of the active ingredients in tobacco can mimic the effects of ACh and increase (or decrease at high doses) autonomic ganglionic transmission as well as that at the... 

Trimethaphan is an antagonist at nicotinic ganglionic synapses. The drug thus blocks transmission of information through autonomic pathways in a dose-dependent manner. 

The primary pathway of cholinergic transmission in autonomic ganglia is similar to that at the neuromuscular junction of skeletal muscle. The initial depolarization is the result of activation of nicotinic ACh receptors, which are ligand-gated cation channels with properties similar to those found at the neuromuscular junction. Several secondary transmitters or modulators either enhance or diminish the sensitivity of the postganglionic cell to ACh. Ganglionic transmission is discussed in more detail in Chapter 9. 

Acetylcholine acts at both the nicotinic ganglionic receptor (site 4) and at muscarinic receptors on effector cells (site 6) and presynaptic nerve endings (site 5). ACh also interacts with acetylcholinesterase (site 7) but does not influence electrical transmission in axons (site 2). The answer is (A). 

Ganglionic transmission Acetylcholine transmits both sympathetic and parasympathetic impulses from the "preganglionic" neurons in the brain and spinal cord to nicotinic ganglionic (N ) receptors on "postganglionic" neurons of the autonomic nervous system. This occurs in sympathetic ganglia, which are located along the spinal cord, and in parasympa-... 

The basis for the antihypertensive activity of the ganglionic blockers lies in their ability to block transmission through autonomic ganglia (Fig. 20.2C). This action, which results in a decrease in the number of impulses passing down the postganglionic sympathetic (and parasympathetic) nerves, decreases vascular tone, cardiac output, and blood pressure. These drugs prevent the interaction of acetylcholine (the transmitter of the preganglionic autonomic nerves) with the nicotinic receptors on postsynaptic neuronal membranes of both the sympathetic and parasympathetic nervous systems. 

Peripheral Nervous System stimulating the ganglion cells and facilitating the transmission of impulses which at higher doses is changed to a blockade. Small doses of nicotine provokes a release of catecholamines from the adrenal medulla whereas larger doses prevent this release in response to splanchnic nerve stimulation. 

The major action of nicotine consists initially of transient stimulation followed by a more persistent depression of all autonomic ganglia Small doses of nicotine stimulate the ganglion cells directly and may facilitate impulse transmission. When larger doses of the drug are applied, the initial stimulation is followed very quickly by a blockade of transmission. Nicotine also possesses a biphasic action on the adrenal medulla small doses evoke the discharge of catecholamines, and larger doses prevent their release in response to splanchnic nerve stimulation. 

Postsynaptic receptors, including two types of muscarinic receptors and at least one type of peptidergic receptor, have been found in ganglionic synapses, where nicotinic transmission is primary. These receptors may facilitate or inhibit transmission by evoking slow excitatory or inhibitory postsynaptic potentials (EPSPs or IPSPs). 

Nicotine Nicotine has the same effects on nicotinic cholinoceptors in insects as in mammals and probably kills by the same mechanism, ie, excitation followed by paralysis of ganglionic, CNS, and neuromuscular transmission. Treatment is supportive. 

The cholinergic synapses in autonomic ganglia are more complex Each ganglionic cell has many synaptic inputs. The receptors on the postsynaptic membrane differ qualitatively. The ChR principally responsible for the transmission is of the nicotinic type (N-ChR). In addition, there are receptors of muscarinic type (M-ChR see p. 242). 

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