Pituitary adenylate cyclase activating polypeptide innervation of the rat female reproductive tract and the associated paracervical ganglia: Effect of capsaicin

Pituitary adenylate cyclase activating peptide (PACAP) is a novel vasoactive intestinal polypeptide-like peptide which is present in neuronal elements of a number of peripheral organs. PACAP occurs in two forms, PACAP-27 and the C-terminally extended PACAP-38, both derived from the same precursor which in addition gives rise to a structurally-related peptide, PACAP-related peptide. Using specific radioimmunoassays for PACAP-38, PACAP-27 and PACAP-related peptide we found that the three PACAP-precursor-derived peptides were present in tissue extracts from all regions of the rat female genital tract. PACAP-38 was the dominating peptide with the highest concentrations in the Fallopian tube and the ovary. Upon reverse phase high pressure liquid chromatography the immunoreactive material was found to co-elute with synthetic PACAP-38, PACAP-27 and PACAP-related peptide, respectively. By immunohistochemistry, PACAP was shown to be located in varicose nerve fibres associated with blood vessels, smooth muscle and epithelial cells. Within the local paracervical ganglion PACAP-immunoreactive fibres ramified often forming varicose, pericellular plexuses around non-PACAP-positive cell bodies. Also bundles of PACAP-immunoreactive fibres were transversing the ganglion. In the paracervical ganglion of normal rat only a few neuronal cell bodies showed immunostaining for PACAP, but after local colchichine-treatment a moderate number of positive perikarya appeared. The synthesis of PACAP in neurons of the paracervical ganglia was confirmed by in situ hybridization histochemistry with a digoxigenin-labelled cRNA probe. Double immunostaining for PACAP and vasoactive intestinal polypeptide disclosed a partial co-existence of the two peptides in nerve fibres of all tubular organs in the rat female genital tract and in cell bodies and nerve fibres in the paracervical ganglion. After neonatal capsaicin treatment the concentration of immunoreactive PACAP-38 as well as the number and intensity of PACAP-positive nerve fibres were reduced while vasoactive intestinal polypeptide immunoreactivity was unaffected. In conclusion, PACAP-immunoreactive nerve fibres have been demonstrated in all regions of the rat female genital tract associated with blood vessels, smooth musculature and epithelium. In some fibres, which seem to originate in the local paracervical ganglia, PACAP was co-localized with vasoactive intestinal polypeptide. PACAP released from these fibres could alone or in concert with vasoactive intestinal polypeptide play a role in neuroregulation of female reproductive organs acting directly on the musculature and vasculature. Other PACAP-containing fibres are sensory in nature, and some of these might influence ganglionic neurotransmission in the local paracervical ganglia.