Montelukast is used as an alternative to inhaled corticosteroids for mild persistent asthma. It works by blocking which receptor, and this receptor is coupled to which intracellular signalling pathway?

• A CysLT2 receptor coupled to Gi protein → decreased cAMP → bronchospasm
• B CysLT1 receptor coupled to Gq protein → phospholipase C → IP3/DAG → increased intracellular calcium ✓
• C BLT1 (LTB4) receptor coupled to Gi protein → reduced adenylyl cyclase → mast cell degranulation
• D CysLT1 receptor coupled to Gs protein → increased cAMP → airway smooth muscle contraction

Explanation

Montelukast and zafirlukast are selective antagonists of the CysLT1 (cysteinyl leukotriene receptor 1). CysLT1 is a GPCR coupled to the Gq protein, which activates phospholipase C, generating IP3 (inositol trisphosphate) and DAG (diacylglycerol). IP3 raises intracellular calcium in airway smooth muscle cells, causing bronchoconstriction; DAG activates protein kinase C. CysLT2 is a separate receptor with distinct signalling. BLT1 mediates effects of LTB4 (chemoattractant) not bronchoconstriction. Coupling to Gs (cAMP increase) would cause bronchodilation, the opposite of leukotriene action.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.