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Receptors appear to be protein macromolecules on cell membranes, which when activated by an agonist (ACh or norepinephrine) lead to a response by an effector cell. An antagonist is a substance that attaches to the receptor (prevents access of an agonist) but does not elicit a response by the effector cell.

  1. Cholinergic receptors are subdivided into muscarinic (postganglionic nerve endings) and nicotinic (autonomic ganglia, neuromuscular junction) receptors. ACh is the neurotransmitter at cholinergic receptors. Atropine is a specific antagonist at muscarinic receptors.
  2. Adrenergic receptors are subdivided into α, β, and dopaminergic, with subtypes for each category (Table 15-2: Adrenergic Receptors and Order of Potency of Agonists and Antagonists).
    1. α-Adrenergic Receptors in the Cardiovascular System
      1. Coronary arteries. Postsynaptic α 2 receptors predominate in the large epicardial conductance vessels. They contribute about 5% to total coronary artery resistance, which is why phenylephrine has little influence on resistance to blood flow in coronary arteries. Postsynaptic α 2 receptors predominate in small coronary artery resistance vessels. The density of α 2 receptors in the coronary arteries increases in response to myocardial ischemia.
      2. Peripheral Vessels. Presynaptic α 2-vascular receptors mediate vasodilation, and postsynaptic α 1- and α 2-vascular receptors mediate vasoconstriction. Postsynaptic α 2-vascular receptors predominate on the venous side of the circulation. Actions attributed to postsynaptic α 2 receptors include arterial and venous vasoconstriction, platelet aggregation, inhibition of insulin release, inhibition of bowel motility, and inhibition of antidiuretic hormone release.
    2. α Receptors in the Kidneys. The α 1 receptors dominate in the renal vasculature (vasoconstriction modulates renal blood flow), and the α 2 receptors predominate in the renal tubules, especially the loops of Henle (which stimulate water and sodium excretion).
    3. β Receptors in the Cardiovascular System
      1. Myocardium. Postsynaptic β 1 receptors and presynaptic β 2 receptors probably play similar roles in the regulation of heart rate and myocardial contractility. Increased circulating catecholamine levels associated with congestive heart failure result in downregulation of β 1 receptors with relative sparing of β 2 and α 1 receptors. (β 2 and α 1 receptors increasingly mediate the inotropic response to catecholamines during cardiac failure.)
      2. Peripheral Vessels. Postsynaptic vascular βreceptors are predominantly β 2.
    4. βReceptors in the Kidneys. β1 receptors are more prominent than βreceptors in the kidneys, and their activation results in renin release.
  3. Adrenergic Receptor Numbers and Sensitivity
    1. Receptors are dynamically regulated by a variety of conditions (ambient concentrations of catecholamines and drugs and genetic factors), resulting in altered responses to catecholamines and ANS stimulation.
    2. Alteration in the number or density of receptors is referred to as upregulation or downregulation. Chronic treatment with clonidine or propranolol results in upregulation and a withdrawal syndrome if the drug is acutely discontinued.

Outline

Autonomic Nervous System: Physiology and Pharmacology

  1. Functional Anatomy
  2. Autonomic Nervous System Transmission
  3. Receptors
  4. Autonomic Nervous System Reflexes and Interactions
  5. Clinical Autonomic Nervous System Pharmacology
  6. Nonadrenergic Sympathomimetic Agents
  7. Sympatholytic Drugs
  8. Calcium Channel Blockers
  9. Angiotensin-Converting Enzyme Inhibitors
  10. Vasodilators