Regulation of vasoactive intestinal peptide receptor expression in developing nervous systems

Bahri Karacay; M. Sue O'Dorisio; Monica Summers; Jarrod Bruce

doi:10.1111/j.1749-6632.2000.tb06963.x

Back

Regulation of vasoactive intestinal peptide receptor expression in developing nervous systems

Journal article

Peer reviewed

Regulation of vasoactive intestinal peptide receptor expression in developing nervous systems

Bahri Karacay, M. Sue O'Dorisio, Monica Summers and Jarrod Bruce

Annals of the New York Academy of Sciences, Vol.921(1), pp.165-174

2000

DOI: 10.1111/j.1749-6632.2000.tb06963.x

PMID: 11193820

View Online

Abstract

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that has several functions, including the regulation of water and electrolyte secretion, hormone and cytokine release, bronchodilitation, and neurogenesis. VIP effects are mediated by specific G-protein coupled receptors. Three distinct receptor subtypes, with differing affinity for VIP, have been cloned and characterized as receptors 1 and 2 (VPAC1 and VPAC2) and pituitary adenylate cyclase activating polypeptide receptor (PAC1). Our laboratory has demonstrated that upregulation of VPAC1 in SK-N-SH neuroblastoma cells results in marked shift in cell type to the glial lineage with a corresponding loss of neuronal lineage and suppression of xenograft tumor growth. To understand the molecular mechanisms responsible for regulation of the VPAC1 gene in neuronal lineage, we have cloned and sequenced 2.6-kb of the 5'-flanking sequences of the human VPAC1 gene. Sequence analysis demonstrated that the human VPAC1 promoter sequence contains putative binding sites for several known transcription factors, including Sp1, NFkB, and cETS-1. To study the temporal and spatial expression pattern of human VPAC1 promoter sequences, we have generated transgenic mice expressing the bacterial beta-galactosidase gene under the control of the 2.6-kb 5'-flanking and promoter sequence of the human VPAC1 gene. Transgene expression was detected in brain, spinal cord, and lung in 14-day-old animals. Taken together, these results demonstrate that VPAC1 may play an important role in the nervous system, and suggest a role for VIP in neuronal differentiation.

Promoter Regions, Genetic

Escherichia coli - enzymology

Spinal Cord - metabolism

Humans

Nervous System - metabolism

Male

Mice, Transgenic

DNA Primers - genetics

Receptors, Vasoactive Intestinal Peptide - genetics

Brain - metabolism

Animals

Nervous System - growth & development

Escherichia coli - genetics

Gene Expression Regulation, Developmental

Base Sequence

Cloning, Molecular

Female

Lung - metabolism

Mice

beta-Galactosidase - genetics

Genes, Reporter

Lac Operon

Receptors, Vasoactive Intestinal Polypeptide, Type I

Details

Title: Subtitle: Regulation of vasoactive intestinal peptide receptor expression in developing nervous systems
Creators: Bahri Karacay - Department of Pediatrics and Comprehensive Cancer Center, Ohio State University, College of Medicine and Public Health, Columbus, Ohio, USA
M. Sue O'Dorisio
Monica Summers
Jarrod Bruce
Resource Type: Journal article
Publication Details: Annals of the New York Academy of Sciences, Vol.921(1), pp.165-174
DOI: 10.1111/j.1749-6632.2000.tb06963.x
PMID: 11193820
NLM abbreviation: Ann N Y Acad Sci
ISSN: 0077-8923
eISSN: 1749-6632
Publisher: Blackwell Publishing Ltd; United States
Grant note: R01CA64177 / NCI NIH HHS
Language: English
Date published: 2000
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984065831802771

Metrics

13 Record Views

5 Times Cited - Web of Science