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The Marshall W. Nirenberg Papers

Title:
Laboratory project: "Regulation of Cyclic Nucleotide Biosynthesis by Neurotransmitters and Opiates" pdf (174,778 Bytes) transcript of pdf
Laboratory project: "Regulation of Cyclic Nucleotide Biosynthesis by Neurotransmitters and Opiates"
Description:
Summary of work on this project as indicated on the report: "The role of the cyclic nucleotides adenosine 3'5' monophosphate and guanosine 3'5' monophosphate in synaptic transmission is under study using cultured cells of neutral origin. The topics of interest during the current year have been the following: 1) The receptor-mediated inhibition of adenylate cyclase activity by alpha-adrenergic agents in neuroblastoma x glioma hybrid cells; 2) Demonstration of a compensatory induction of adenylate cyclase activity in cells treated for one or more days with alpha-adrenergic agents, as had been previously demonstrated by others for opiates, and study of the mechanism of this compensatory induction; 3) The effect of opiates and alpha-adrenergic agents on guanosine 3'5' monophosphate levels in the hybrid cells; 4) Search for a cultured-cell system which synthesizes a peptide with opiate-like properties."
Item is a photocopy.
Number of Image Pages:
2 (174,778 Bytes)
Date:
1976-09 (September 1976)
Creator:
Nirenberg, Marshall W.
Sabol, Steven L.
National Heart and Lung Institute. Laboratory of Biochemical Genetics
Rights:
This item is in the public domain. It may be used without permission.
Exhibit Categories:
From Neuroblastoma to Homeobox Genes, 1976-1992
Neuroblastoma Research, 1967-1976
Relation:
Metadata Record Annual Report of the Laboratory of Biochemical Genetics, October 1, 1975 - September 30, 1976 (September 1976)
Box Number:
31 of 31
Unique Identifier:
JJBBPD
Accession Number:
2001-020
Document Type:
Reports
Excerpts
Language:
English
Format:
application/pdf
image/tif
Physical Condition:
Good
Transcript:
Project Number: Z01 HL 00015-01 LBG
Period Covered: July 1, 1975 through June 30, 1976
Title of Project: Regulation of cyclic nucleotide biosynthesis by neurotransmitters and opiates
Names, Laboratory and Institute Affiliations, and Titles of Principal Investigators and All Other Professional Personnel Engaged on the Project:
PI: Marshall Nirenberg, Chief, Lab. of Biochem. Genetics, LBG NHLI
Steven L. Sabol, Research Associate, LBG NHLI
Cooperating Units (if any): None
Lab/Branch: Laboratory of Biochemical Genetics
Section: Section on Molecular Biology
Institute and Location: NHLI, NIH, Bethesda, Maryland 20014
Total Man Years: 2.0
Professional: 1.5
Other: .5
Summary of Work: The role of the cyclic nucleotides adenosine 3'5' monophosphate and guanosine 3'5' monophosphate in synaptic transmission is under study using cultured cells of neural origin. The topics of interest during the current year have been the following: 1) The receptor-mediated inhibition of adenylate cyclase activity by alpha-adrenergic agents in neuroblastoma x glioma hybrid cells; 2) Demonstration of a compensatory induction of adenylate cyclase activity in cells treated for one or more days with alpha-adrenergic agents, as had been previously demonstrated by others for opiates, and study of the mechanism of this compensatory induction; 3) The effect of opiates and alpha-adrenergic agents on guanosine 3'5' monophosphate levels in the hybrid cells; 4) Search for a cultured-cell system which synthesizes a peptide with opiate-like properties.
Project Description:
Objectives: Previous work in this laboratory demonstrated that opiates, alpha-adrenergic agonists, and muscarinic cholinergic agonists lower cyclic AMP (adenosine 3'5' monophosphate) levels by receptor-mediated mechanisms in the neuroblastoma x glioma hybrid cell line NG108-15. Also demonstrated was the inhibition of adenylate cyclase by opiates and a compensatory induction of adenylate cyclase activity (measured in the absence of opiates) in cells grown in the presence of opiates. One aspect of the present project attempts to demonstrate and analyze similar effects of adrenergic agonists on adenylate cyclase in cell-free systems. Another aspect is to relate these findings to the action of the enkephalins, recently discovered endogenous opiate-like peptides.
Major Findings: (1) Adrenergic agents, like opiates, inhibit adenylate cyclase activity in NG108-15 homogenates. The order of agonist potencies is consistent with an alpha receptor, and the effect is blocked by alpha receptor antagonists.
(2) Cultivation of NG108-15 with norepinephrine for 1 to 4 days results, as in the case with opiates, in an increase in adenylate cyclase activity which compensates for the inhibition of this enzyme by norepinephrine. Cells then appear tolerant to norepinephrine, but are dependent upon norepinephrine for maintenance of normal cAMP levels. Withdrawal of norepinephrine or the addition of an alpha-adrenergic antagonist results in an increase in cellular cyclic AMP levels to abnormally high values.
Significance to Biomedical Research: The results show that cells exposed to alpha-receptor activators for several days become tolerant to and dependent upon these compounds and that tolerance and dependence are established by the mechanism of dual regulation of adenylate cyclase.
Proposed Course: It is intended to continue the investigation of the induction of adenylate cyclase activity by cyclase inhibitors, including the possible mediation of cyclase activators. Also the relationship among the opiate, adrenergic and cholinergic receptors in NG108-15 should be studied. Finally a search for endogenous "endorphin" synthesis in cell lines of neural origin is being initiated, with the goal of developing a tissue culture system for the study of the biosynthesis of this peptide or peptides.
Metadata Last Modified Date:
2010-10-04
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