Mutants of PC12 cells with altered cyclic AMP responses
PCl2 cells, derived from a rat pheochromocytoma, were mutagenized and selected in media containing agents known to elevate intracellular concentrations of cyclic AMP (cAMP). More than 40 clones were isolated by selection with cholera toxin or 2-chloroadenosine or both. The variants that were deficient in accumulating cAMP were obtained by using a protocol in which 1 ..mu..m 8-bromo-cAMP was included in addition to the agonist. Certain of these variants were partially characterized with respect to the site of altered cAMP metabolism. The profiles of adenylate cyclase activity responsiveness of certain variants to guanosine-5'-(BETA,..gamma..-imido) triphosphate and to forskolin resembled those of UNC and cyc phenotypes of S49 lymphoma cells, which are functionally deficient in the GTP-sensitive coupling protein, N/sub s/. Other variants were characterized by increased cyclic nucleotide phosphodiesterase activity at low substrate concentration. Diverse morphological traits were observed among the variants, but it was not possible to assign them to a particular cAMP phenotype. Two revertants of a PCl2 mutant were isolated and observed to have regained a cellular cAMP response to 2-chloroadenosine and to forskolin. It is hoped that these PCl2 mutants will have utility for defining cAMP-mediated functions, including any links to the action of nerve growth factor, in cells derived from the neural crest.
- Research Organization:
- Dept. of Pharmacology, Univ. of Medicine and Dentistry of New Jersey, Rutgers Medical School, Piscataway, NJ 08854
- OSTI ID:
- 5877922
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 4:10
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AMP
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
PHYSIOLOGY
CYCLASES
ENZYME INDUCTION
PHOSPHODIESTERASES
DEFECTS
ADENOSINE
ADENYLIC ACID
ADRENAL GLANDS
CELL CULTURES
CHLORINE COMPOUNDS
CHOLERA
CULTURE MEDIA
GUANOSINE
LYMPHOMAS
MUTANTS
PHENOTYPE
PHOSPHATES
RATS
TOXINS
TUMOR CELLS
ANIMAL CELLS
ANIMALS
ANTIGENS
AROMATICS
AZAARENES
BACTERIAL DISEASES
BODY
DISEASES
ENDOCRINE GLANDS
ENZYMES
ESTERASES
GENE REGULATION
GLANDS
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
HYDROLASES
INFECTIOUS DISEASES
LYASES
MAMMALS
MATERIALS
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHOSPHORUS COMPOUNDS
PURINES
RIBOSIDES
RODENTS
SYNTHESIS
TOXIC MATERIALS
VERTEBRATES
550400* - Genetics