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Nursing Pharmacology Chapter 5: Autonomic Pharmacology: Cholinergic Drugs
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Cholinergic Receptors: Subtypes, Tissues, Responses and Molecular Mechanisms
Muscarinic Receptor Coupling Mechanisms
Five types of cholinergic receptors have been identified by molecular cloning methods.
The five muscarinic receptor subtypes, M1 - M5, are associated with specific anatomical sites. For example:
M1 -ganglia; secretory glands
M2 - myocardium, smooth muscle
M3 , M4 :smooth muscle, secretory glands
| Antagonists | Tissue | Responses | Molecular Aspects |
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Tubocurarine α-bungarotoxin |
Neuromuscular Junction |
Membrane Depolarization leading to muscle contraction |
Nicotinic (muscle) receptor's ion channel opening |
| Antagonists | Tissue | Responses | Molecular Aspects |
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Mecamylamine (Inversine) |
Autonomic Ganglia |
Depolarization: postsynaptic cell activation |
Nicotinic (muscle) receptor's ion channel opening |
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Adrenal Medulla |
Catecholamine secretion |
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CNS |
unknown |
| Antagonist | Tissue | Responses | Molecular Aspects |
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Atropine Pirenzepine (more selective) |
Autonomic Ganglia |
Depolarization (late EPSP) |
Stimulation of Phospholipase C leading to increased cytosolic Ca2+ |
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CNS |
Unknown |
| Tissue (Heart) | Responses | Molecular Aspects |
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SA node |
decreased phase 4 depolarization; hyperpolarization |
K+ channel activation through ß-gamma Gi subunits; Gi -mediated inhibition of adenylyl cyclase which decreases intracellular Ca2+ levels. (Gi can inhibit directly Ca2+ channel opening) |
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Atrium |
decreased contractility; decreased AP duration |
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AV node |
decreased conduction velocity |
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Ventricle |
decreased contractility |
Adapted from Table 6-2: Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, p119.
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