Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates adenylyl cyclase and phospholipase C activity in rat cerebellar neuroblasts

J Neurochem. 1995 Sep;65(3):1318-24. doi: 10.1046/j.1471-4159.1995.65031318.x.


The presence of receptors for the novel neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been recently demonstrated in the external granule cell layer of the cerebellum, a germinative matrix that generates the majority of cerebellar interneurons. In the present study, we have taken advantage of the possibility of obtaining a culture preparation that is greatly enriched in immature cerebellar granule cells to investigate the effect of PACAP on the adenylyl cyclase and phospholipase C transduction pathways. The two molecular forms of PACAP, i.e., 27-(PACAP27) and 38-(PACAP38) amino-acid forms of PACAP, induced a dose-dependent stimulation of cyclic AMP production in granule cells. The potencies of PACAP27 and PACAP38 were similar (ED50 = 0.12 +/- 0.01 and 0.23 +/- 0.07 nM, respectively), whereas vasoactive intestinal polypeptide (VIP) was approximately 100 times less potent. PACAP27 and PACAP38 also induced a dose-dependent stimulation of polyphosphoinositide breakdown (ED50 = 19.1 +/- 6.3 and 13.4 +/- 6.0 nM, respectively), whereas VIP had no effect on polyphosphoinositide metabolism. The effect of PACAP38 on inositol phosphate formation was significantly reduced by U-73122 and by pertussis toxin, indicating that activation of PACAP receptors causes stimulation of a phospholipase C through a pertussis toxin-sensitive G protein. In contrast, forskolin and dibutyryl cyclic AMP did not affect PACAP-induced stimulation of inositol phosphates. Taken together, the present results demonstrate that PACAP stimulates independently the adenylyl cyclase and the phospholipase C transduction pathways in immature cerebellar granule cells. These data favor the concept that PACAP may play important roles in the control of proliferation and/or differentiation of cerebellar neuroblasts.

MeSH terms

  • Adenylate Cyclase Toxin
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Cells, Cultured
  • Cerebellum / drug effects
  • Cerebellum / enzymology*
  • Cyclic AMP / biosynthesis
  • Estrenes / pharmacology
  • Inositol Phosphates / metabolism
  • Neuropeptides / pharmacology*
  • Pertussis Toxin
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism*
  • Vasoactive Intestinal Peptide / pharmacology
  • Virulence Factors, Bordetella / pharmacology


  • Adcyap1 protein, rat
  • Adenylate Cyclase Toxin
  • Estrenes
  • Inositol Phosphates
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Pyrrolidinones
  • Virulence Factors, Bordetella
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Vasoactive Intestinal Peptide
  • Cyclic AMP
  • Pertussis Toxin
  • Type C Phospholipases
  • Adenylyl Cyclases