D-Serine modulates neurogenic relaxation in rat corpus cavernosum

Abstract

d-Serine, an endogenous co-agonist for the N-methyl- d-aspartate (NMDA) receptor in mammals, is synthesized from l-serine by serine racemase. Although much attention has been focused on the role of d-serine within the central nervous system, the physiological role of d-serine in peripheral nerves such as corpus cavernosal nerves has not been investigated. The present study was aimed to study the expression, cellular localization and function of serine racemase/ d-serine system in isolated rat corpus cavernosum. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis showed the expression of serine racemase in rat corpus cavernosum. Immunogold electron microscopy demonstrated the cellular localization of serine racemase in the cavernosal nerves’ membrane of the tissue. The organ bath studies on isolated rat corpus cavernosum showed that d-serine increases the non-adrenergic non-cholinergic neurogenic relaxation of isolated rat corpus cavernosum in vitro. This effect of d-serine was inhibited by a variety of NMDA receptor antagonists (ketamine, MK 801 and ifenprodil), suggesting that NMDA receptors are involved in the effects of d-serine on the neurogenic relaxation of corporal tissue strips. These observations provide the first evidence for the role of d-serine in modulating the neurogenic relaxation of rat corpus cavernosum, and may open new therapeutic avenues for the treatment of impotence.