Lubiprostone, used for chronic idiopathic constipation and IBS-C, works by activating which channel/receptor in intestinal epithelial cells?

• A ClC-2 chloride channels (CFTR-independent) causing chloride and fluid secretion into the intestinal lumen ✓
• B EP4 prostaglandin receptor triggering cAMP-mediated fluid secretion in the colon
• C Guanylyl cyclase C (GC-C) receptor generating cGMP that activates CFTR chloride channels
• D NHE3 (sodium-hydrogen exchanger 3) blockade reducing sodium and water absorption in the jejunum

Explanation

Lubiprostone is a bicyclic fatty acid derived from prostaglandin E1 that selectively activates ClC-2 (type 2 chloride channels) on the apical surface of intestinal epithelial cells. ClC-2 activation allows chloride efflux into the intestinal lumen; this creates an osmotic gradient that draws water into the lumen, softening stool and increasing intestinal transit. Importantly, ClC-2 is independent of CFTR (mutated in cystic fibrosis), distinguishing lubiprostone's mechanism from linaclotide. Linaclotide activates GC-C receptors producing cGMP that activates CFTR (option C). NHE3 inhibition (tenapanor) is used for IBS-C and hyperphosphatemia.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.