THE PRESENCE OF NERVE-FIBERS IMMUNOREACTIVE FOR VASOACTIVE-INTESTINAL-PEPTIDE (VIP), PEPTIDE HISTIDINE ISOLEUCINE (PHI), AND PREPROVIP(111-122) IN THE MOUSE PINEAL-GLAND

A low to moderate number of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI)-immunoreactive nerve fibers with prominent boutons-en-passage were demonstrated in the pineal gland of the mouse. The two peptides, which are parts of the same precursor molecule, were distributed identically in the gland. Positive fibers were present in the connective tissue septae in the gland, in the pineal capsule, and in the pineal parenchyma. No VIP-PHI-immunoreactive elements were found in the deep pineal gland, in the pineal stalk, or in habenular and posterior commissures. This morphological distribution of immunoreactive nerve fibers, which is similar to the distribution in other mammals, indicates that the VIP/PHI fibers of the mouse pineal gland originate exclusively from perikarya in a peripheral ganglion, presumably one of the cholinergic ganglia of the head. No evidence for a VIPergic central innervation was found. VIP and PHI are connected via a bridging peptide equivalent to amino acids 111-122 of the precursor (preproVIP(111-122)). In order to demonstrate the possible existence of this peptide in intra-pineal nerve fibers, antisera directed against a synthetic sequence identical to preproVIP(111-122) and immunohistochemistry were applied. PreproVIP(111-122)-immunoreactive nerve fibers were observed in the mouse pineal gland, with the same distribution pattern and morphology as those immunoreactive for VIP and PHI. To quantify the peptide-immunoreactivities, 50 mice pineals were pooled, extracted, and the concentrations were measured radioimmunologically. The concentrations of the VIP and preproVIP(111-122) immunoreactivities were 1.7 and 2.0 pmol/g, respectively, whereas the concentration of PHI was 0.9 pmol/g. This indicates that not only VIP and PHI, but also other fragments of preproVIP are present in the mammalian pineal gland. Whereas the stimulatory role of VIP is well documented, the effect of other fragments processed from preproVIP on pinealocytes remains to be established.