Biosynthetic processing of preprovasoactive intestinal polypeptide in parasympathetic neurons of the sphenopalatine ganglion.

The precursor for rat vasoactive intestinal polypeptide (preproVIP) is processed by proteolytic cleavage into a signal peptide and five further functional domains: preproVIP 22-79, peptide histidine isoleucine (PHI), preproVIP 111-122, VIP, and preproVIP 156-170. To investigate the biosynthetic processing of preproVIP in peripheral parasympathetic neurons, the sphenopalatine ganglion and one of its projection areas, the nasal mucosa, were used. By immunohistochemistry it was shown that in the sphenopalatine ganglion, preproVIP-derived peptides are localized mainly in neuronal cell bodies, whereas in the nasal mucosa immunoreactivity was found only in nerve fibers and terminals. The peptides were quantified and characterized by radioimmunoassay, HPLC, and gel chromatography using antisera specific for the different precursor products. In the rat sphenopalatine ganglion, the different peptides were found in approximately equimolar amounts, with the exception of PHI and its C-terminally extended variant, PHV, which were present at considerably lower concentrations. However, in the nasal mucosa there was a preferential accumulation of VIP to at least three times the concentration of any of the other peptides. Our results suggest that all preproVIP-derived peptides are present and processed in the sphenopalatine ganglion but that there is a selective accumulation of VIP in the nerve terminals. This indicates that VIP is physiologically the most important transmitter among the preproVIP-derived peptides in parasympathetic nerves originating in the sphenopalatine ganglion.