Adrenal medulla, nicotinic stimulation

Like in the neuromuscular junction the neurotransmission can be inhibited either by receptor blockade (non-depolarizing) or by overstimulation (depolarizing) of the receptors. The alkaloid nicotine, in low doses, stimulates ganglia and the adrenaline release from the adrenal medulla. High doses lead to a continuous depolarization of the postsynaptic membrane and thereby to an inactivation of the neurotransmission. All ganglion blockers in clinical use were synthetic amines of the nondepolarizing type trimethaphan, hexamethonium and mecamylamide. 

In addition to autonomic ganglia, nicotinic receptors are found in a variety of organs, and their stimulation will produce quite different results in these different tissues. Activation of nicotinic receptors on the plasma membrane of the cells of the adrenal medulla leads to the exo-cytotic release of epinephrine and norepinephrine stimulation of nicotinic receptors at the neuromuscular junction results in the contraction of skeletal muscle (see... 

The effects of nicotine on the cardiovascular system mimic those seen after activation of the sympathoadrenal system, and they are principally the result of a release of epinephrine and norepinephrine from the adrenal medulla and adrenergic nerve terminals. These effects include a positive inotropic and chronotropic effect on the myocardium as well as an increase in cardiac output. In addition, both systohc and diastolic blood pressures are increased secondary to stimulation of the sympathoadrenal system. These effects are the end result of a summation of adrenergic and chohnergic stimulation. 

Nicotine is a tertiary amine compound composed of a pyridine and a pyrrolidine ring. It binds selectively to acetylcholine receptors at the autonomic ganglia in the adrenal medulla at neuro-muscular junction and in the brain. It exerts a stimulating effect in the cortex and a reward effect via the pleasure system in the limbic system. 

Acetylcholine receptors are classified as either muscarinic cholinergic receptors or nicotinic cholinergic receptors. The alkaloid muscarine mimics the effects produced by stimulation of the parasympathetic system. These effects are postganglionic and are exerted on exocrine glands, cardiac muscle, and smooth muscle. The alkaloid nicotine mimics the actions of acetylcholine, which include stimulation of all autonomic ganglia, stimulation of the adrenal medulla, and contraction of skeletal muscle. 

Actions Carbachol has profound effects on both the cardiovascular system and the gastrointestinal system because of its ganglion-stimulating activity and may first stimulate and then depress these systems. It can cause release of epinephrine from the adrenal medulla by its nicotinic action. Locally instilled into the eye, it mimics the effects of acetylcholine, causing miosis. 

Tobacco smoke includes 4000 chemical species with varying potential which cause adverse effects. Nicotine is stimulating to the autonomic nervous system ganglia and neuromuscular junction. The most prominent effects relate to stimulation of the adrenal medulla, central nervous system (CNS), cardiovascular system (release of catecholamines), gastrointestinal tract (parasympathetic stimulation), salivary and bronchial glands, and the medullary vomiting center. There is subsequent blockade of autonomic ganglia and the neuromuscular junction transmission, inhibition of catecholamine release from the adrenal medulla, and CNS depression. 

Table 11-2-2 summarizes the effects of nicotinic receptor activation on the adrenal medulla, the autonomic ganglia, and the neuromuscular junction. The effect of autonomic ganglia stimulation depends upon the transmission system used to conned the ganglia to the end organ. Blood vessels are innervated by SANS, resulting in vasoconstriction. PANS innervates the gut, the end result being increased motility and secretion. 

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. 

In general, the cardiovascular responses to nicotine are due to stimulation of sympathetic ganglia and the adrenal medulla, together with the discharge of catecholamines from sympathetic nerve endings. Also contributing to the sympathomimetic response to nicotine is the activation of chemoreceptors of the aortic and carotid bodies, which reflexly results in vasoconstriction, tachycardia, and elevated blood pressure. 

Dixon (46) has discussed the oldest works on cytisine intoxication. The most detailed experiments were carried out by Dale and Laidlaw (102). Cytisine like nicotine provokes an excitation of mammalian muscle which is at least partially central in origin because section of the spinal cord diminishes its intensity. This alkaloid renders the muscles insensitive to the stimulation of the motor nerve (6-10 mg.). Cytisine provokes hypertension when it is injected intravenously. Like nicotine, after having stimulated the peripheral sympathetic ganglia, it paralyzes them and does not act after these ganglia have been paralyzed by nicotine. The hypertension is partially dependent on a liberation of adrenaline from the adrenal medulla (103). 

Raymond-Hamet (172) observed that hordenine, like nicotine, provokes a contracture and then a relaxation of the small intestine. It causes a liberation of adrenaline from the adrenal medulla which can be detected by several physiological methods, as for instance by adrenal-jugular anastomoses. Large doses of hordenine abolish the effects of vagal stimulation and those of nicotine on the heart, on the arterial pressure, and on the small gut in situ, but it does not modify the bradycardia caused by acetylcholine, nor the hypertensor effects of adrenaline. 

Histrionicotoxin noncompetitively inhibits nicotine-stimulated secretion of catecholamines from adrenal medulla cells 164), suggesting similar interactions of the alkaloid with the nicotinic acetylcholine receptor channel complex in both adrenal medulla and in muscle., ... 

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