CALCITONIN-GENE-RELATED PEPTIDE (CGRP) AND ITS EFFECTS ON PROTEIN RELEASE IN-VITRO IN THE DEVELOPING SUBMANDIBULAR-GLAND OF THE RAT

Indirect immunohistochemical methods were used to study presence and n umber of CGRP-immunoreactive (CGRP-IR) nerve fibers in the submandibul ar gland and ganglion cells of the superior cervical, submandibular an d trigeminal ganglia of the developing rat, The effect of CGRP on pero xidase and total protein release was also studied in the developing po stnatal submandibular glands of 1, 5, 12 and 30-day-old, as well as ad ult rats by in vitro methods. The possible costimulation of CGRP with SP, NKA or carbachol on 5-day-old and adult rats was also tested. The stimulatory effects of these compounds were compared to the basic rele ase of peroxidase and total amount of proteins from submandibular glan d fragments in incubation solution, CGRP-IR nerve fibers were found in relatively high number during post-natal development, mainly around b lood vessels and ducts. Some CGRP-IR nerve fibers were also detected a round acini. The number of these fibers was quite low and remained con stant during the post-natal development. The number of CGRP-IR trigemi nal ganglion cells was higher on the 5th and 12th post-natal day than later in development and in adult animals. At the same time, superior cervical- and submandibular ganglion cells were non-reactive for CGRP, suggesting trigeminal origin of CGRP-IR nerve fibers during the devel opment in the submandibular gland. In the secretory studies, CGRP per se stimulated both peroxidase and total protein release in the submand ibular gland most effectively on 5th and 12th post-natal days, while t here was no clear secretory response in the adult glands. In the 5-day -old submandibular gland CGRP in combination with SP, NKA or carbachol clearly enhanced the total protein secretory response when compared w ith the release caused by these substances alone. However, in the adul t submandibular gland, the combinations did not enhance total protein release more than any of the substances alone. Furthermore, it can be concluded that the presence of a more dense CGRP-IR innervation during the early postnatal period in the developing submandibular gland is a ccompanied with an increased responsiveness of the secretory elements to CGRP.