Expression of genes for metabolism of cyclic adenosine 3'

5' monophosphate in somatic cells. I. Responses to catecholamines in parental and hybrid cells

A. G. Gilman, J. D. Minna

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The effects of catecholamines (norepinephrine and isoproterenol) on the intracellular accumulation of cyclic adenosine 3':5' monophosphate (cyclic AMP) were determined for clonal cell lines cultured in vitro. Catecholamine responsive (β+) and unresponsive (β-) clones were found. β+ responses were inhibited selectively by propranolol (1 μM) but not by practolol (10 μM), indicating that the response should be classified as β2 +. These cell lines were then used as parents in somatic cell hybridization to study the genetic control of the β2 + response. In general, β2 + x β2 + matings yielded β2 + hybrid cells, while β2+ x β- matings yielded β- hybrid cells (less than 2% of the β2 + parental response). However, β2 + parental cells with large responses (300 fold stimulation) to catecholamine, when fused to β2 + parents with smaller (15 fold stimulation) responses, yielded hybrids with definite but minimal (average of 3 fold) stimulation. Chromosome analysis of all hybrid cells revealed no evidence for preferential loss of marker chromosomes of the β2 + parent. These data represent evidence for a heritable negative control mechanism regulating catecholamine responsiveness. In addition, the hybrid cell lines represent new biologic material for biochemical study of the macromolecular events between β adrenergic stimulation and the accumulation of intracellular cyclic AMP.

Original languageEnglish (US)
Pages (from-to)6610-6617
Number of pages8
JournalJournal of Biological Chemistry
Volume248
Issue number19
StatePublished - 1973

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Hybrid Cells
Metabolism
Adenosine
Catecholamines
Genes
Gene Expression
Cells
Chromosomes
Cell Line
Practolol
Chromosomes, Human, Pair 2
Isoproterenol
Propranolol
Adrenergic Agents
Norepinephrine
Clone Cells
Cyclic AMP

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "Expression of genes for metabolism of cyclic adenosine 3': 5' monophosphate in somatic cells. I. Responses to catecholamines in parental and hybrid cells",
abstract = "The effects of catecholamines (norepinephrine and isoproterenol) on the intracellular accumulation of cyclic adenosine 3':5' monophosphate (cyclic AMP) were determined for clonal cell lines cultured in vitro. Catecholamine responsive (β+) and unresponsive (β-) clones were found. β+ responses were inhibited selectively by propranolol (1 μM) but not by practolol (10 μM), indicating that the response should be classified as β2 +. These cell lines were then used as parents in somatic cell hybridization to study the genetic control of the β2 + response. In general, β2 + x β2 + matings yielded β2 + hybrid cells, while β2+ x β- matings yielded β- hybrid cells (less than 2{\%} of the β2 + parental response). However, β2 + parental cells with large responses (300 fold stimulation) to catecholamine, when fused to β2 + parents with smaller (15 fold stimulation) responses, yielded hybrids with definite but minimal (average of 3 fold) stimulation. Chromosome analysis of all hybrid cells revealed no evidence for preferential loss of marker chromosomes of the β2 + parent. These data represent evidence for a heritable negative control mechanism regulating catecholamine responsiveness. In addition, the hybrid cell lines represent new biologic material for biochemical study of the macromolecular events between β adrenergic stimulation and the accumulation of intracellular cyclic AMP.",
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AU - Minna, J. D.

PY - 1973

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AB - The effects of catecholamines (norepinephrine and isoproterenol) on the intracellular accumulation of cyclic adenosine 3':5' monophosphate (cyclic AMP) were determined for clonal cell lines cultured in vitro. Catecholamine responsive (β+) and unresponsive (β-) clones were found. β+ responses were inhibited selectively by propranolol (1 μM) but not by practolol (10 μM), indicating that the response should be classified as β2 +. These cell lines were then used as parents in somatic cell hybridization to study the genetic control of the β2 + response. In general, β2 + x β2 + matings yielded β2 + hybrid cells, while β2+ x β- matings yielded β- hybrid cells (less than 2% of the β2 + parental response). However, β2 + parental cells with large responses (300 fold stimulation) to catecholamine, when fused to β2 + parents with smaller (15 fold stimulation) responses, yielded hybrids with definite but minimal (average of 3 fold) stimulation. Chromosome analysis of all hybrid cells revealed no evidence for preferential loss of marker chromosomes of the β2 + parent. These data represent evidence for a heritable negative control mechanism regulating catecholamine responsiveness. In addition, the hybrid cell lines represent new biologic material for biochemical study of the macromolecular events between β adrenergic stimulation and the accumulation of intracellular cyclic AMP.

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