Functional and pathological consequences of being fast on the uptake: Protein kinase G and p38α MAPK regulation of serotonin transporters.

Serotonin (5-hydroxytryptamine, 5-HT) signaling plays an important role in dynamic control of peripheral and central nervous system physiology, with altered 5-HT homeostasis implicated in a significant number of disorders, ranging from pulmonary, bowel, and metabolic disease to depression, obsessive-compulsive disorder, and autism spectrum disorder (ASD). The presynaptic, 5-HT transporter (SERT) has a well-established role in regulating 5-HT signaling and is a target of widely prescribed psychotherapeutics, the 5-HT selective reuptake inhibitors (SSRIs). Although SSRI therapy provides symptom relief for many suffering from mood and anxiety disorders, response to these medications is slow (weeks), and too many receive modest or no benefit.