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.
- 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.
- 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).
- α-Adrenergic Receptors in the Cardiovascular System
- 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.
- 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.
- 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).
- β Receptors in the Cardiovascular System
- 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.)
- Peripheral Vessels. Postsynaptic vascular βreceptors are predominantly β
2.
- βReceptors in the Kidneys. β1 receptors are more prominent than βreceptors in the kidneys, and their activation results in renin release.
- Adrenergic Receptor Numbers and Sensitivity
- 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.
- 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.