Part of “CHAPTER 85 – PHYSIOLOGY OF THE ADRENAL MEDULLA AND THE SYMPATHETIC NERVOUS SYSTEM“

Specific receptors for catecholamines exist in several tissues, including muscle (skeletal, myocardial, vascular, gastrointestinal, ciliary, and bronchial) and glands (salivary, sweat, adrenocortical, and pancreatic).24 These receptors mediate the effects of endogenously released as well as exogenously administered catecholamines (Table 85-1).

Ahlquist25 introduced the concept of α- and β-adrenergic receptors to explain contrasting cardiovascular responses to exogenous catecholamines. NE administration causes diffuse vasoconstriction and reflexive bradycardia, whereas EPI causes vasodilation of skeletal muscle beds, tachycardia, and increased myocardial contractility. According to this framework, the vasoconstrictor actions of NE and EPI result from stimulation of α-adrenergic receptors, whereas the cardiotonic, tachycardiac, and vasodilator properties of EPI result from stimulation of β-adrenergic receptors.

Further subclassification to α₁-, α₂-, β₁-, and β₂-adrenergic receptors has been based on ligand-binding studies, on responses to synthetic agonists and antagonists, and on molecular genetic experiments.26,27 and 28 NE is an agonist at β₁-, α₁-, and α₂–adrenergic receptors, whereas EPI is an agonist at all four subtypes. Stimulation of α₁-receptors causes vasoconstriction. Phenylephrine is an example of a relatively specific α₁-agonist, and prazosin is an example of an α₁-antagonist. α₂-Selective agonists, such as clonidine hydrochloride,29 α-methyldopa, and guanabenz,30 exert more complex effects, because stimulation of α₂-receptors on vascular smooth muscle cells elicits vasoconstriction and increased blood pressure, whereas stimulation of presynaptic α₂-receptors inhibits NE release from sympathetic nerve endings, and stimulation of α₂-receptors in the central nervous system causes decreases in sympathetic outflow and increases in vagal outflow. The latter effects predominate, and α₂-agonists are used as antihypertensive medications. α₂-Antagonists (e.g., yohimbine) cause increases in plasma NE, as well as a psychiatric pattern of heightened arousal and tremulousness, in contrast with the sedation induced by α₂-agonists. Pharmacologic and molecular genetic studies have demonstrated the existence of several subtypes of α₂-adrenoceptors. The structure of the subtype responsible for modulation of NE release from sympathetic nerves remains unknown.