Male Reproductive Tract

Protein Inhibitor of Nitric Oxide Synthase (NOS) and the N-Methyl-D-Aspartate Receptor Are Expressed in the Rat and Mouse Penile Nerves and Colocalize with Penile Neuronal NOS

Abstract

Nitrergic neurotransmission triggering penile erection is mediated by nitric oxide (NO) synthesized in the cavernosal nerves of the penis by penile neuronal nitric oxide synthase (PnNOS). In the CNS, nNOS is activated by the N-methyl-D-aspartate receptor (NMDAR), and presumably inhibited by the protein inhibitor of NOS, PIN. PnNOS and NMDAR are expressed in the penis, and PnNOS has been localized in penile nerves. Both proteins colocalize with PIN in the hypothalamus and the spinal cord involved in the control of erection. The present work aimed to elucidate the relationship between PnNOS, PIN, and NMDAR in the penis. It was found that: 1. in the rat, PIN is expressed in the pelvic ganglion and the cavernosal nerve; and penile PIN cDNA was cloned, sequenced, and expressed; 2. immunohistochemistry has localized PIN to the cavernosal and dorsal nerve of the penis, whereas NMDAR was not detected in the latter; 3. dual fluorescence labeling showed that PnNOS co-localizes with PIN in both nerves, but with NMDAR only in the cavernosal nerve; 4. aging did not affect the mRNA levels of PnNOS, nNOS, NMDAR, and PIN; 5. both PIN and NMDAR were detected in penile nerves of the wild type and nNOS^-/- mouse; 6. PIN protein did not inhibit or bind NOS in penile extracts; 7. in vivo, PIN cDNA reduced the erectile response to electrical field stimulation. In conclusion, PIN and NMDAR co-localize with PnNOS in penile nerves, but the functional significance of these protein interactions for penile erection still remains to be elucidated.