Secretoneurin, rat

Proteolytic processing of secretogranin II (chromogranin C) in brain leads to the formation of a 33-amino acid peptide which we have named secretoneurin. All the properties of secretoneurin are consistent with the concept that this peptide represents a neuropeptide. However, a biological function has not yet been demonstrated. Therefore, we have now investigated whether secretoneurin could alter transmitter release in brain. Slices of rat caudate-putamen were superfused in an in vitro system and dopamine was measured in the superfusate. Secretoneurin dose-dependently increased the outflow of dopamine. This response was abolished in Ca(2+)-free medium. The secretoneurin-response could also be blocked by preincubation of the peptide with a specific antiserum and was subject to rapid specific and reversible desensitization. This effect on dopamine release constitutes the first discovered biological effect found for a peptide derived from secretogranin II. Thus, secretoneurin can be added to the ever-growing number of neuropeptides.

Secretoneurin is a 33-amino acid peptide derived from secretogranin II. Secretoneurin immunoreactivity has been localized in the peripheral nervous system where it exerts potent chemotactic activity for monocytes and may play a role in inflammation. Secretoneurin could play a role in this process, although the presence and distribution of secretoneurin-immunoreactive neurons in the female reproductive system has not been documented. Thus, this study was undertaken to examine secretoneurin immunoreactivity in nerves of the rat uterus and uterine cervix. A moderate plexus of secretoneurin-immunoreactive nerve fibers was present in the myometrium and endometrium of the uterus as well as in the smooth muscle and endocervix of the cervix. Many of these fibers were associated with the vasculature as well as the myometrium. Secretoneurin immunoreactivity was present in small- to medium-sized neurons of dorsal root and nodose ganglia. Retrograde tracing with FluoroGold indicated that some of these sensory neurons project axons to the cervix and uterine horns. Secretoneurin-immunoreactive terminal-like structures were associated with neurons in the sacral parasympathetic nucleus of the lumbosacral spinal cord. In addition, some secretoneurin terminals were apposed to pelvic parasympathetic neurons in the paracervical ganglia that projected axons to the uterus and cervix. Double-immunostaining indicated co-existence of calcitonin gene-related peptide or substance P with secretoneurin in some sensory neurons, in some terminals of the pelvic ganglia, as well as nerve fibers in the uterine horn and cervix. Finally, fibers in the uterus and cervix were depleted of secretoneurin by capsaicin treatment. This study indicates that secretoneurin is present in the uterus in C-afferent nerve fibers whose cell bodies are located in sensory ganglia. Some of these fibers contain both secretoneurin and calcitonin gene-related peptide or substance P. These substances have functions in inflammatory reactions. Further, secretoneurin could influence postganglionic parasympathetic "uterine-related" neurons in the pelvic ganglia and preganglionic parasympathetic neurons in the lumbosacral spinal cord.

Secretoneurin is a 33-amino acid peptide, generated in brain by proteolytic processing of secretogranin II. The distribution of secretoneurin-like immunoreactivity and secretogranin II mRNA was investigated in the hippocampus of the rat. Secretogranin II mRNA was found in high concentrations throughout the granule cell and pyramidal cell layers and in many local neurons, notably in the hilus of the dentate gyrus. The general distributional pattern of secretoneurin-like immunoreactivity was characterized by a prominent staining in the area of the terminal field of mossy fibers with an obvious staining in the infrapyramidal area of CA3 and a strongly immunopositive band in the inner third of the molecular layer of the dentate gyrus. Lesions of the granule cells by local injection of colchicine significantly reduced secretoneurin-like immunoreactivity in the terminal field of mossy fibers, but not in the inner molecular layer of the dentate gyrus. On the other hand, destruction of interneurons of the dentate gyrus (mossy cells and certain gamma-aminobutyricacid-ergic interneurons) by kainic acid-induced seizures was associated with a reduction of secretoneurin-like immunoreactivity in the inner molecular layer of the dentate gyrus. However, 30 days after kainic acid-induced seizures, a strongly secretoneurin-immunoreactive band reappeared in this area, which at this late time point is due to sprouting of mossy fibers collaterals. Our experiments suggest a widespread distribution of secretoneurin-like immunoreactivity in neurons of the hippocampal formation with a preferential localization in excitatory pathways including associational/commissural fibers originating from secretoneurin-containing mossy cells.