Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase

Purpose: To characterize the distribution of cholinergic nerves in the huma n corpus cavernosum (CC) and spongiosum (CS) using antibodies to the vesicu lar acetylcholine transporter (VAChT), and to compare this distribution to those of other transmitters/mediators or transmitter/mediator generating en zymes theme oxygenases: HO-1 and HO-2; neuronal and endothelial NO synthase s: nNOS and eNOS; vasoactive intestinal polypeptide: VIP; and tyrosine hydr oxylase: TH), and to investigate NO- and carbon monoxide (CO)-mediated effe cts. Materials and Methods: Immunocytochemistry, confocal laser scanning microsc opy, radioimmunoassay, and functional in vitro studies. Results: Along strands of smooth muscle in the CC and CS, rich numbers of V AChT-, nNOS-, VIP-, TH-, and very few HO-1-immunoreactive (-IR) nerve fiber s were observed. Immunoreactivities for VAChT and nNOS, VAChT and VIP, and nNOS and VIP, were generally found in the same varicose nerve terminals. TH -IR nerve fibers or terminals did not contain immunoreactivities for VAChT, NOS or VIP. In the endothelium lining penile arteries, immunoreactivities for eNOS, HO-1, and HO-2 were detected. Single endothelial cells, lining th e sinusoidal walls of the CC and CS, were found also to contain eNOS and HO -immunoreactivities. Noradrenaline (NA)-contracted preparations of CC and C S were relaxed by NO, CO, carbachol and by electrical stimulation of nerves . Inhibition of NO synthesis abolished electrically- and carbachol-induced relaxation. In NA-activated strips, relaxation induced by exogenously appli ed NO, but not those by CO, were accompanied by increases in intracellular levels of cyclic GMP. Conclusions: VAChT, NOS and VIP are found in the same nerve terminals withi n the human CC and CS, suggesting that these terminals comprise a distinct population of parasympathetic, cholinergic nerves. Endothelially derived NO and the HO/CO system may have a complementary role in penile erection.