Synthesis, Storage and Destruction of 5 Hydroxytryptamine

SYNTHESIS, STORAGE AND DESTRUCTION

5HT is βaminoethyl5hydroxyindole. It is synthesized from the amino acid tryptophan and degraded primarily by MAO and to a small extent by a dehydrogenase (Fig. 12.1).

There is close parallelism between CAs and 5HT. The decarboxylase is nonspecific, acts on DOPA as well as 5hydroxytryptophan (5HTP) to produce NA and 5HT respectively. Like NA, 5HT is actively taken up by an amine pump serotonin transporter (SERT), a Na+ dependent carrier, which operates at the membrane of platelets (therefore, 5HT does not circulate in free form in plasma) and serotonergic nerve endings. This is inhibited by selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. Platelets do not synthesize but acquire 5HT by uptake during passage through intestinal blood vessels. Again like CAs, 5HT is stored within storage vesicles, and its uptake at the vesicular membrane by vesicular monoamine transporter (VMAT2) is inhibited by reserpine, which causes depletion of CAs as well as 5HT. The degrading enzyme MAO is also common for both. The isoenzyme MAOA preferentially metabolizes 5HT.