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

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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.",
author = "Gilman, {A. G.} and Minna, {J. D.}",
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T2 - 5' monophosphate in somatic cells. I. Responses to catecholamines in parental and hybrid cells

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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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