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GIITHSONIAN SCI  NCE  lNFORMATlON EXCHANGE     U.S. DEPAATMEIIT OF       PROJECT NUMECR
PROJECT NUMBER  Do NOT use this space)   HEALTH EDUCATlO'l AN0 WELFARE
                      PbSLlC HEALTk SERVICE
                                    NOTICE OF
                            INTRAMURAL RESEARCH PROJECT    201 HL 00016-01 LBG

PERIOD COVERED

July 1, 1975 through June 30, 1976
TITLE OF PROJECT (80 characters or less)

Acetylcholine Receptor-Mediated Regulation of Adenylate Cyclase in Hybrid Cell5

NA?riES, 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
     Neil M. Nathanson        Guest Worker             LBG NHLI

COOPERATING UNITS (if any)

Muscular Dystrophy Association

LAi3/8RANCH
Laboratory of Biochemical Genetics
SECTION

Section on Molecular Biology
INSTITUTE AND LOCATION
NJ&I, NIH, Bethesda, Maryland 20014
TOTAL MANYEARS:       1 PROFESS I ONAL:

IOTHER:

   1.05       I    1.05      I
SU?rlMARY OF WORK (200 words or less - underline keywords)

I    The activity of adenylate cyclase in neuroblastoma x glioma hybrid NG108-15
cells is regulated by the interaction of acetylcholine and its analogues with I
the muscarinic acetylcholine receptors of the cells.  Addition of the acetyl-
choline analogue carbamylcholine inhibits adenylate cyclase activity.  However,
growth of cells with carbachol results in a prolonged increase in adenylate
cyclase activity.  Adenylate cyclase activity increases slowly and after 18-24
hours is 1.5-3 times higher than control values.  Intracellular CAMP is also
1.5-3-fold higher in carbachol-grown cells than in controls. These changes are
maintained for at least three days in the presence of carbachol, but the activ-
ity returns to control values if carbachol is removed.



I                             I
PHI;-fro40


201 HL 00016-01 LBG

Project Description:

   Objectives:  The objective of this project is to study muscarinic acetyl-
choline-receptor mediated regulation of adenylate cyclase activity, in an at-
tempt to understand how neurotransmitter-receptor interactions modulate synap-
tic transmission.

   Major Findings:  The activity of adenylate cyclase in neuroblastoma x
glioma hybrid NG108-15 cells is regulated by the interaction of acetylcholine
and its analogues with the muscarinic acetylcholine receptors of the cells.
Addition of the acetylcholine analogue carbamylcholine inhibits adenylate cy-
,clase activity.  However, growth of cells with carbachol-results in a prolonged
increase in adenylate cyclase activity.  Adenylate cyclase activity increases
slowly and after 18-24 hours is'l.S-3 times higher than control values.  Intra-
cellular CAMP is also l.S-3-fold higher in carbachol-grown cells than in
controls.  These changes are maintained for at least three days in the presence
of carbachol, but the activity returns to control values if carbachol is re-
moved.

   Significance to Biomedical Research:  The results obtained suggest that
neurotransmitter-receptor interactions can exert long-lived effects on macro-
molecules required for synaptic transmission.

   Proposed Course:  Work on this project will be incorporated into other
projects in the coming year.