Which receptor-mediated effect of opioids accounts for constipation in many patients?

• A. Mu receptor activation decreases GI motility and secretions.
• B. Delta receptor activation increases GI motility.
• C. Kappa receptor activation enhances GI secretions.
• D. Mu receptor blockade increases GI motility.

Answer: (A)

Mu receptor activation in the enteric nervous system slows gut movement and reduces secretions. When opioids bind these receptors in the GI tract, they inhibit excitatory signaling to smooth muscle and decrease acetylcholine release, which lowers propulsive motility. They also dampen secretory activity, making stools drier. The combination of slower propulsion and drier contents leads to constipation, a common opioid side effect. Delta and kappa receptor actions in the gut are not the main drivers of this effect, and blocking mu receptors would relieve the constipation by reversing the inhibitory influence on motility and secretion.