Neurturin is a neurotrophic factor for penile parasympathetic neurons in adult rat

Neurturin (NRTN), a member of the GDNF family of neurotrophic factors, prom otes the survival and function of several neuronal populations in the perip heral and central nervous system. Recent gene ablation studies have shown t hat NRTN is a neurotrophic factor for many cranial parasympathetic and ente ric neurons, whereas its significance for the sacral parasympathetic neuron s has not been studied. NRTN signals via a receptor complex composed of the high-affinity binding receptor component GFR alpha 2 and the transmembrane tyrosine kinase Ret. The aim of this study was to determine whether NRTN c ould be an endogenous trophic factor for penis-projecting parasympathetic n eurons. NRTN mRNA was expressed in smooth muscle of penile blood vessels an d corpus cavernosum in adult rat as well as in several intrapelvic organs, whereas GFR alpha 2, and Ret mRNAs were expressed in virtually all cell bod ies of the penile neurons, originating in the major pelvic ganglia, I-125-N RTN injected into the shaft of the penis was retrogradely transported into the major pelvic and dorsal root ganglia, Mice lacking the GFR alpha 2 rece ptor component had significantly less nitric oxide synthase-containing nerv e fibers in the dorsal penile and cavernous nerves. In conclusion, these da ta suggest that NRTN acts as a target-derived survival and/or neuritogenic factor for penile erection-inducing postganglionic neurons. (C) 2000 John W iley & Sons, Inc. J Neurobiol 43: 198-205, 2000.