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 - Dec 1 1973

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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