Presence of NMDA receptor subunits in the male lower urogenital tract

Some sexual responses in the male rat, specifically penile erection, are co ntrolled by neural circuits in the brain and spine that are stimulated by t he binding of excitatory amino acids (EAAs) to the postsynaptic N-methyl-D- aspartate receptor (NMDAR). In the hypothalamus, EAA/NMDAR interaction trig gers the activation of neuronal nitric oxide synthase (nNOS) to produce nit ric oxide (NO). The local synthesis of this neurotransmitter in the penile nerve terminals causes corpora cavernosal relaxation and erection. During s exual activity, NO is assumed to participate in seminal emission and ejacul ation in the prostate and to inhibit voiding reflexes in the bladder. This study aimed to determine in vitro whether NMDAR is present in these organs and whether it affects the tone of tissue strips through an NO-dependent me chanism. We obtained penile, urinary bladder, and ventral prostate tissues from adult male rats and homologous surgical tissues from human male patien ts. We detected the NMDAR protein by Western blot and determined the bindin g of the NMDA antagonist, 3H-CGP. The NMDAR messenger ribonucleic acid (mRN A) was detected by reverse transcription/polymerase chain reaction and iden tified by cloning and sequencing. The in vitro response to NMDAR antagonist s was measured in tissue strips that were precontracted with bethanechol or electrical field stimulation tin rat and human bladder), phenylephrine tin human corpora cavernosa), or norepinephrine tin human prostate). The NMDAR 2B protein; ligand-binding activity; and NMDAR1, 2A, and 2B mRNAs were dete cted in all tissues studied. We found an NMDAR1 variant in rat prostate and penis and in human prostate that is larger than its cerebellar counterpart , but it encodes a 767-amino acid truncated protein (NMDAR1 -T). The in vit ro contraction of tissue strips was inhibited by NMDAR antagonists against the following sites: polyamine (with ifenprodil); ion channnel high affinit y (with dizocilpine); ion channel low affinity (with memantidine, dextromet orphan, and ketamine); and, in an NO-independent, nonadrenergic-noncholiner gic pathway that was only partially affected by EAAs. We conclude that, in vitro, all the essential NMDAR subunits are present in the lower urogenital tract, a novel variant of subunit 1 is expressed, the tissues bind an NMDA R ligand, and the NMDAR antagonists induce relaxation of tissue strips. Fur ther work is necessary to determine whether the NMDAR subunits form a fully active receptor and participate in the control of organ tone that is relev ant to male sexual activity.