Receptors and transmission in the brain-gut axis: Potential for novel therapies - I. Receptors on visceral afferents

Visceral afferents are the information superhighway from the gut to the cen tral nervous system. These sensory nerves express a wide range of membrane receptors that can modulate their sensitivity. In this themes article, we c oncentrate on those receptors that enhance the excitability of visceral aff erent neurons. Some receptors are part of a modality-specific transduction pathway involved in sensory signaling. Others, which are activated by subst ances derived from multiple cellular sources during ischemia, injury, or in flammation, act in a synergistic fashion to cause acute or chronic sensitiz ation of the afferent nerves to mechanical and chemical stimuli. Such hyper sensitivity is the hallmark of conditions such as irritable bowel syndrome. Accordingly, these receptors represent a rational target for drug treatmen ts aimed at attenuating both the inappropriate visceral sensation and the a berrant reflex activity that are the foundation for alterations in bowel fu nction.