Guanylate Cyclase-C Receptor Agonists

Guanylate cyclase-C receptor agonists are indicated in the treatment of irritable bowel syndrome with constipation.  Stimulation of guanylate cyclase-C receptors results in increased gut motility and decreases visceral hypersensitivity.  

Class Drugs

• Linaclotide

Class Mechanism of Action

Constipation:

Stimulates guanylate cyclase-C receptor (GCC) in gut lumen. GCC signaling cascade activates the cystic fibrosis transmembrane conductance regulator (CFTR) that promotes secretion of bicarbonate and chloride ions and inhibits absorption of sodium. This cascade results in increased intestinal fluid, which increases gut motility.

Intestinal cramping:

Increases in cGMP levels (from GCC receptor activation) also inhibit gut nociceptors, which reduces intestinal discomfort/pain.

Class Applications

Irritable bowel syndrome with constipation

Class Adverse Effects

Diarrhea

Abdominal Discomfort

Drug Table

Drug Name	Application	Comments	Image
Linaclotide			"Line" "Clot" "Tide"