Pituitary adenylate cyclase activating polypeptide prevents apoptosis in cultured cerebellar granule neurons.

Abstract:

:The two forms of pituitary adenylate cyclase-activating polypeptide, PACAP27 and PACAP38, are two neuropeptide hormones related to the vasoactive intestinal peptide/secretin/ glucagon family of peptides. PACAP receptors that are positively coupled to adenylyl cyclase and phospholipase C have been identified in cultured cerebellar granule cells. Using the reverse transcription-polymerase chain reaction methodology, we demonstrated the expression of the PACAP-R and PACAP-R-hop mRNAs in cultured granule cells. When grown in the absence of serum or in low K+ concentrations, these neurons underwent apoptosis, a naturally occurring process characterized by cell shrinkage and internucleosomal DNA cleavage. We used these models of programmed cell death to study the relationship between PACAP receptor activation and neuronal apoptosis. Treatment with PACAP27 and PACAP38 reduced the development of apoptosis in a dose-dependent manner. The neuroprotective activity of PACAP was mimicked by high concentrations of vasoactive intestinal peptide or forskolin but not by carbamylcholine. Thus, we suggest that the activation of type I PACAP receptors may contribute to the survival of cerebellar granule neurons.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Cavallaro S,Copani A,D'Agata V,Musco S,Petralia S,Ventra C,Stivala F,Travali S,Canonico PL

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

60-6

issue

1

eissn

0026-895X

issn

1521-0111

journal_volume

50

pub_type

杂志文章