Chapter 5  ·  Module 1  ·  Visual Summary

Adrenergic Receptors

Classification · Signaling · Tissue Distribution · Regulation

Receptor Subtypes & G-Protein Coupling

Alpha-1

Gq → IP3 / Calcium

CascadePhospholipase C-beta → IP3 → calcium release
EffectSmooth muscle contraction
LocationsVascular smooth muscle, iris dilator, urethral sphincter, prostate

Alpha-2

Gi → Decreased cyclic AMP

CascadeInhibits adenylyl cyclase → decreased cyclic AMP
Key sitePresynaptic autoreceptor → reduces norepinephrine release
DrugsClonidine, dexmedetomidine (agonists); yohimbine (antagonist)

Beta-1

Gs → Increased cyclic AMP

HeartIncreased rate, contractility, conduction (chronotropy / inotropy / dromotropy)
KidneyRenin release from juxtaglomerular cells
DrugsMetoprolol, atenolol (selective blockers)

Beta-2

Gs → Increased cyclic AMP

BronchiBronchodilation — target of albuterol, salmeterol
UterusRelaxation — terbutaline as tocolytic
MetabolicGlycogenolysis; potassium shift into cells (hypokalemia)

Beta-3

Gs → Restricted Distribution

AdiposeLipolysis and thermogenesis
BladderDetrusor relaxation — target of mirabegron
NoteResistant to desensitization; not targeted by standard adrenergic drugs

Dopamine — Dose-Dependent Receptor Engagement

Dose Range Receptor Engaged Clinical Effect
Low (~1–3 mcg/kg/min) D1 Renal and mesenteric vasodilation; natriuresis. Does not protect against acute kidney injury.
Moderate (~3–10 mcg/kg/min) Beta-1 Increased cardiac output; positive inotropy and chronotropy
High (>10 mcg/kg/min) Alpha-1 Systemic vasoconstriction; profile resembles norepinephrine; arrhythmia risk increases

Receptor Regulation — Three Clinical Scenarios

Beta-2 Agonist Tachyphylaxis

Chronic albuterol overuse → beta-2 receptor downregulation → reduced bronchodilation. Fix: inhaled corticosteroids as controller; short-acting agonist for rescue only.

Beta-Blocker Withdrawal

Chronic blockade → beta-1 upregulation → abrupt stop → rebound tachycardia / angina / myocardial infarction risk. Always taper over 1–2 weeks.

Heart Failure Remodeling

Chronic norepinephrine excess → beta-1 downregulation → impaired contractile reserve. Beta-blockers (carvedilol, metoprolol succinate) reverse this over months.