Phenylephrine is used as a nasal decongestant. When applied topically, which receptor subtype does it primarily activate and what is the molecular consequence in vascular smooth muscle cells?

• A Alpha-1 receptors → Gq/phospholipase C activation → IP3-mediated Ca2+ release → calmodulin-myosin kinase complex → vasoconstriction ✓
• B Beta-1 receptors → increased cAMP → protein kinase A activation → myosin light chain phosphorylation
• C Alpha-2 receptors → Gi inhibition of adenylyl cyclase → decreased cAMP → protein kinase A inhibition → vasoconstriction
• D Beta-2 receptors → Gs activation → increased cAMP → vasoconstriction via unique smooth muscle pathway

Explanation

Phenylephrine is a selective alpha-1 adrenoceptor agonist. Alpha-1 receptors couple to Gq protein which activates phospholipase C-beta. This generates IP3 (inositol trisphosphate) and DAG (diacylglycerol). IP3 triggers Ca2+ release from the sarcoplasmic reticulum, elevating cytoplasmic Ca2+, which binds calmodulin. The Ca2+-calmodulin complex activates myosin light chain kinase (MLCK), phosphorylates myosin light chains, allowing actin-myosin crossbridge formation and smooth muscle contraction (vasoconstriction and mucosal decongestant effect).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.