Four peptides - vasoactive intestinal polypeptide, substance P, somatostatin and a peptide-like avian pancreatic polypeptide - have been found in nerves of the human male genitalia using highly sensitive and specific methods of immunocytochemistry and radioimmunoassay. Five other peptides (met-enkephalin, leu-enkephalin, neurotensin, bombesin and cholecystokinin-8) were absent. Vasoactive intestinal polypeptide was the most abundant peptide, its highest concentration being in the proximal corpus cavernosum. Immunoelectron microscopy localized this peptide to large (97 ± 20 nm), round, electron-dense granules of p-type nerve terminals. Vasoactive intestinal polypeptide-immunoreactive neuronal cell bodies were found in the prostate gland and the root of the corpus cavernosum. Substance P immunoreactive mateerial was present in smaller concentration and was mainly localized in nerves around the corpuscular receptors of the glans penis. Somatostatin immunoreactive nerves were associated mainly with the smooth muscle of the seminal vesicle and the vas deferens. When antiserum to avian pancreatic polypeptide was applied, certain nerves were stained, particularly in the vas deferens, the prostate gland and the seminal vesicle. However, chromatography detected no pure avian pancreatic polypeptide suggesting the presence of a structurally related substance, possibly neuropeptide Y, which cross-reacts with the avian pancreatic polypeptide antiserum. Similar distributions between vasoactive intestinal polypeptide-immunoreactive and acetylcholinesterase-positive nerves and between avian pancreatic polypeptide-immunoreactive and adrenergic nerves were observed. A general neuronal marker, neuron-specific enolase, was used to investigate the general pattern of the organ's innervation. The abundance and distribution patterns of these peptide-immunoreactive nerves indicate that they may play important roles in the male sexual physiology.
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