Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) and the PACAP-selective receptor in cultured rat astrocytes, human brain tumors, and in response to acute intracranial injury

Cell Tissue Res. 2000 May;300(2):219-30. doi: 10.1007/s004410000184.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Astrocytes / metabolism*
  • Brain Injuries / metabolism*
  • Brain Neoplasms / metabolism*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Neuropeptides / biosynthesis*
  • Oligodendroglioma / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Pregnancy
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Pituitary Hormone / biosynthesis*
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Receptors, Vasoactive Intestinal Polypeptide, Type I
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • ADCYAP1 protein, human
  • ADCYAP1R1 protein, human
  • Adcyap1 protein, rat
  • Adcyap1r1 protein, rat
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Pituitary Hormone
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Receptors, Vasoactive Intestinal Polypeptide, Type I
  • VIPR1 protein, human
  • VIPR2 protein, human
  • Vipr1 protein, rat
  • Vipr2 protein, rat