Antagonism of VIP-stimulated cyclic AMP formation in chick brain

Jerzy Z. Nowak, Paulina Sedkowska, Jolanta B. Zawilska, Illana Gozes, Douglas E. Brenneman

Research output: Contribution to journalArticlepeer-review

Abstract

Of eight peptides tested (0.01-5 μM), only two, that is, pituitary adenylate cyclase-activating polypeptide (PACAP27) and chicken vasoactive intestinal peptide (cVIP), potently stimulated cyclic AMP (cAMP) production in cerebral cortical slices of the chick. Mammalian VIP (mVIP) showed some activity only at the highest dose tested, whereas truncated forms of PACAP or VIP, that is, PACAP6-27, cVIP6-28, and mVIP6-28, or hybrid compounds, that is, neurotensin6-11-cVIP7-28 (NT-cVIP) and neurotensin6-11-mVIP7-28 (NT-mVIP), were inactive. Thirty-minute preincubation of chick cortical slices with 5 μM PACAP6-27, NT-cVIP, or NT-mVIP competitively antagonized the cAMP effects of cVIP (0.03-1μM), with the truncated form of PACAP being the best antagonist. Preincubation of slices with 5 μM mVIP6-28 also produced a significant inhibition of the cVIP (0.1-1 μM)-induced increase in cAMP production; however its action was independent of the concentration of cVIP. In contrast to mVIP6-28, cVIP6-28 showed no antagonistic activity against the full-length peptide. In parallel experiments, 30-min pretreatment of cortical slices with 5 μM PACAP6-27 significantly antagonized the PACAP38-evoked increase in cAMP formation, whereas mVIP6-28 or the NT-mVIP hybrid was ineffective. It has been concluded that in the chick brain, PACAP and cVIP stimulate cAMP biosynthesis via PAC1 and VPAC-type receptors, respectively, and PACAP6-27 seems to be the most potent, yet PACAP/VIP receptor-nonselective antagonist. Unlike truncated PACAP, the NT-VIP hybrid peptides tested may represent VPAC-type receptor-selective blocking activity.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalJournal of Molecular Neuroscience
Volume20
Issue number2
DOIs
StatePublished - Apr 2003

Keywords

  • Chick cerebral cortex
  • Cyclic AMP (cAMP)
  • PACAP
  • PACAP antagonist
  • VIP
  • VIP antagonist

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