What are the types of autonomic receptors and their functions relevant to the Physician Licensure Exam (PLE)?

Types of Autonomic Receptors: A Review for the Physician Licensure Exam

Adrenergic Receptors

Alpha-Adrenergic Receptors

• Alpha-1 receptors are primarily postsynaptic receptors that mediate vasoconstriction in blood vessels through G-protein coupled mechanisms, resulting in increased vascular resistance and blood pressure 1, 2
• Alpha-2 receptors are primarily presynaptic and inhibit norepinephrine release, functioning as a negative feedback mechanism to regulate sympathetic outflow 2, 3
• Alpha-adrenergic receptors are single polypeptides with molecular mass of approximately 85,000 Da and an isoelectric point of 4.6 2
• Phenylephrine is a selective α-1 adrenergic receptor agonist that increases systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and total peripheral vascular resistance 1

Beta-Adrenergic Receptors

• Beta-1 receptors are predominantly found in the heart and mediate increased heart rate (chronotropic effect), contractility (inotropic effect), and conduction velocity (dromotropic effect) 4, 2
• Beta-2 receptors are located primarily in bronchial and vascular smooth muscle, mediating bronchodilation and vasodilation 2, 3
• Beta-3 receptors are found in adipose tissue and mediate lipolysis 3
• Beta-adrenergic receptors are single polypeptides with molecular mass of approximately 68,000 Da and an isoelectric point of 5.0 2
• Propranolol is a nonselective beta-adrenergic receptor blocker that competes with beta-adrenergic receptor-stimulating agents for available receptor sites, decreasing chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation 4

Cholinergic Receptors

Nicotinic Acetylcholine Receptors

• Ganglionic (α3-type) nicotinic receptors are ligand-gated cation channels that mediate fast synaptic transmission in sympathetic, parasympathetic, and enteric autonomic ganglia 5
• Neuromuscular junction (α1-type) nicotinic receptors mediate skeletal muscle contraction 5
• Antibodies against ganglionic acetylcholine receptors can cause autoimmune autonomic ganglionopathy (AAG), resulting in autonomic failure with orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, and bladder dysfunction 5

Muscarinic Acetylcholine Receptors

• M1 receptors are found in the CNS and autonomic ganglia 2, 6
• M2 receptors are predominantly cardiac, mediating decreased heart rate and contractility 6
• M3 receptors are located in smooth muscle and glands, mediating contraction of smooth muscle and increased glandular secretions 6
• M4 and M5 receptors are primarily found in the CNS 6
• Muscarinic cholinergic receptors are single polypeptides with molecular mass of approximately 80,000 Da and an isoelectric point of 4.2 2

Autonomic Receptor Function in Cardiovascular Regulation

Vascular Control

• Alpha-1 adrenergic receptor activation causes vasoconstriction in most vascular beds, including renal, splanchnic, and hepatic 1
• Beta-2 adrenergic receptor activation causes vasodilation 3
• The balance between alpha and beta receptor activation determines vascular tone and blood pressure 3, 6

Cardiac Control

• Parasympathetic stimulation via M2 muscarinic receptors decreases heart rate, atrioventricular conduction, and contractility 6
• Sympathetic stimulation via beta-1 adrenergic receptors increases heart rate, conduction velocity, and contractility 4, 6
• The Valsalva maneuver demonstrates autonomic control of cardiovascular function, with sympathetic outflow to blood vessels increasing and parasympathetic outflow to the heart decreasing during phase II 7

Autonomic Testing

• Deep-breathing test evaluates parasympathetic function, with heart rate normally rising during inspiration and falling during expiration (respiratory sinus arrhythmia) 7
• Heart rate variability during deep breathing is modulated by cardiac parasympathetic (vagal) outflow and is blunted or abolished in patients with cardiovascular autonomic failure 7
• Plasma catecholamine measurements can indicate sympathetic noradrenergic and adrenomedullary hormonal system activity but have limited diagnostic value due to their sensitivity to lifestyle factors 7

Autonomic Receptor Dysfunction

Orthostatic Hypotension

• Classical orthostatic hypotension is characterized by a sustained reduction in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg within 3 minutes of standing 7
• Delayed orthostatic hypotension occurs beyond 3 minutes of standing 7
• Orthostatic hypotension can result from impaired sympathetic vasoconstriction due to autonomic failure 7

Postural Orthostatic Tachycardia Syndrome (POTS)

• POTS is characterized by an excessive increase in heart rate upon standing without orthostatic hypotension 7
• Laboratory evaluation should include thyroid function tests, complete blood count, basic metabolic panel, and cardiac biomarkers to rule out secondary causes 8

Autoimmune Autonomic Ganglionopathy

• Autoantibodies against the neuronal acetylcholine receptors in autonomic ganglia can cause dysautonomia 7, 5
• Symptoms include orthostatic hypotension, GI dysmotility, anhidrosis, bladder dysfunction, and sicca symptoms 7, 5

Autonomic Receptors in Gastrointestinal Function

GI Motility Regulation

• Parasympathetic stimulation via muscarinic receptors generally increases GI motility 9
• Sympathetic stimulation via alpha adrenergic receptors generally decreases GI motility 9
• GLP-1 receptors on the myenteric plexus activate nitrergic and cyclic adenosine monophosphate pathways to inhibit vagal activity on the gut, leading to reduced gastric contractions and delayed emptying 9

Secretory Regulation

• Autonomic innervation regulates gastric acid secretion, with increased fasting and postprandial gastric volumes observed with vagal stimulation 9
• Parasympathetic stimulation increases secretion from digestive glands 9

Clinical Implications

Pharmacological Targets

• Beta-blockers like propranolol compete with beta-adrenergic receptor-stimulating agents for available receptor sites, decreasing chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation 4
• Alpha-1 agonists like phenylephrine increase blood pressure by causing vasoconstriction 1
• Understanding receptor function is critical for appropriate drug selection in various clinical scenarios 4, 1, 6

Diagnostic Applications

• Autonomic function testing helps characterize cardiovascular sympathetic and parasympathetic autonomic function 7
• The Valsalva maneuver evaluates both sympathetic and parasympathetic function 7
• Deep-breathing test specifically evaluates parasympathetic function 7

Understanding the types and functions of autonomic receptors is essential for diagnosing and treating disorders of autonomic function, as well as for understanding the mechanisms of action of many commonly used medications.