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Publication : Concentrations and distribution of vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI) and peptide histidine valine (PHV) in the cerebral cortex and the suprachiasmatic nucleus of the mouse.

First Author  Mikkelsen JD Year  1994
Journal  Brain Res Volume  656
Issue  1 Pages  95-107
PubMed ID  7804850 Mgi Jnum  J:20001
Mgi Id  MGI:68117 Doi  10.1016/0006-8993(94)91370-6
Citation  Mikkelsen JD, et al. (1994) Concentrations and distribution of vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI) and peptide histidine valine (PHV) in the cerebral cortex and the suprachiasmatic nucleus of the mouse. Brain Res 656(1):95-107
abstractText  Prepro-vasoactive intestinal peptide (prepro-VIP) is processed to at least three biologically active peptides: VIP, peptide histidine isoleucine (PHI) and an extended PHI, peptide histidine valine (PHV). The aim of the present investigation was by chromatography combined with RIA and immunocytochemistry to determine which of these peptides were present in the cerebral cortex and the hypothalamic suprachiasmatic nucleus (SCN) of the mouse. These regions were chosen since they are known to contain a high concentration of VIP but the relative concentration of PHI and PHV is not known. Tissue was extracted and subjected to gel chromatography and high-pressure liquid chromatography (HPLC). VIP and PHI immunoreactivities co-eluted with synthetic rat VIP and PHI. A minor peak of PHI and prepro-VIP(111-122) immunoreactivities eluted at the position of synthetic PHV. Surprisingly, a major peak of prepro-VIP(111-122) immunoreactivity eluted in a position not related to any other immunoreactivity indicating the presence of prepro-VIP(111-122). Measurements of these immunoreactivities in cortical and suprachiasmatic extracts revealed that VIP was found in the highest concentration whereas PHV was found in the lowest. Immunoreactivity for PHI and prepro-VIP(111-122) was found in moderate concentrations. Except for prepro-VIP(111-122) which was found to be approximately 3 x higher concentrated in the SCN than in the cerebral cortex, the other immunoreactivities were found in almost similar relative concentrations in the two tissues. Using immunocytochemistry, elongated neurons mostly of the bipolar type with prominent processes observed in the cerebral cortex reacted with all antisera tested. More PHI/PHV/prepro-VIP(111-122)- than VIP-immunoreactive (ir) nerve fibers were found in the cerebral cortex. In the SCN, the density of immunoreactivity was the same whatever antiserum used. VIP-, PHI- and prepro-VIP(111-122)/PHV-ir neurons were observed in the ventral part of the nucleus with numerous axons coursing caudodorsally into the subparaventricular area. A substantial number of terminals was detected caudal to the paraventricular nucleus. Minor projections spread to the medial part of the anterior nucleus and to the medial preoptic area hypothalamic. These data show that VIP and PHI are the major active peptides derived from prepro-VIP in the mouse cerebral cortex and SCN whereas PHV was found in minor concentrations. Prepro-VIP(111-122), which so far has been found to have no functional significance, is, therefore, most likely a vaste fragment of processing of PHI in central neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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