Ontogeny of the peptidergic fibers in the male mouse submandibular gland.

The first appearance of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), galanin (GAL), leucine-enkephalin (1-ENK), and methionine-enkephalin (m-ENK) in the male mouse submandibular glands were different for each. VIP immunoreactive fibers first appeared on embryonic day 15 (E15), SP on E16, and CGRP fibers on E18. GAL, 1-ENK, and m-ENK fibers appeared in the early postnatal period, and NPY fibers occurred on postnatal day 21 (P21). From P0 to P21, VIP fibers rapidly increased in number, but SP and CGRP fibers increased only slightly. After P21, VIP, SP, and CGRP fibers decreased in number. ENK fibers were found only from P0 to P14. The number of these immunoreactive fibers in the adult phase was low in comparison with that in early postnatal phase. Around the blood vessels, SP, VIP, CGRP, NPY, and GAL fibers appeared by at least P7. These findings suggested that the transient high activity of VIP, CGRP, SP, and GAL and the transient appearance of ENKs in the nerve fibers may be related to the cell proliferation and differentiation of the functionally important structures of the mouse submandibular glands, and that the peptidergic innervation around the vasculature is probably involved in controlling local glandular circulation.