Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a bioactive peptide with diverse activities in the nervous system. In addition to its more classic role as a neurotransmitter, PACAP functions as a neurotrophic factor. PACAP exerts these activities by binding to PACAP-selective (PAC1) or nonselective (VPAC1, VPAC2) receptors (-R). Glial cells also exhibit PACAP binding, which is associated with the increased proliferation of astrocytes. The present report demonstrates a distinct spatiotemporal regulation of PACAP, PAC1-R, VPAC1-R, and VPAC2-R expression in primary cultured rat astrocytes. To determine the role of PACAP and PAC1-R expression on glial proliferation, two in vivo models were examined--human brain tumors of glial origin and the reactive gliosis induced by a penetrating stab wound to the mature rat brain. Relative to normal human brain, PAC1-R expression is significantly upregulated in glioma, particularly oligodendrogliomas. While similar polymerase chain reaction (PCR) analysis does not detect PACAP expression, in situ hybridization studies reveal PACAP expression in a limited number of cells within the tumor. In sharp contrast, neither PACAP nor PAC1-R expression are upregulated consequent to injury. These results suggest a distinct role for PACAP and PAC1-R in glioma development and nervous system response to injury.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Animals
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Astrocytes / metabolism*
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Brain Injuries / metabolism*
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Brain Neoplasms / metabolism*
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Child
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Child, Preschool
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Female
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Humans
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In Situ Hybridization
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Male
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Middle Aged
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Neuropeptides / biosynthesis*
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Oligodendroglioma / metabolism
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Pregnancy
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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Rats
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Rats, Sprague-Dawley
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Receptors, Pituitary Hormone / biosynthesis*
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Receptors, Vasoactive Intestinal Peptide, Type II
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
Substances
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ADCYAP1 protein, human
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ADCYAP1R1 protein, human
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Adcyap1 protein, rat
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Adcyap1r1 protein, rat
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Neuropeptides
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Pituitary Adenylate Cyclase-Activating Polypeptide
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Receptors, Pituitary Hormone
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Receptors, Vasoactive Intestinal Peptide, Type II
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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VIPR1 protein, human
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VIPR2 protein, human
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Vipr1 protein, rat
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Vipr2 protein, rat