Expression of genes for metabolism of cyclic adenosine 3',5' monophosphate in somatic cells. II. The effects of prostaglandin E1 and theophylline on parental and hybrid cells

J. D. Minna, A. G. Gilman

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Abstract

Clonal differences in the response to prostaglandin E1 (PGE1) were found when changes in the intracellular concentration of cyclic adenosine 3':5' monophosphate (cyclic AMP) were measured following exposure to this agent in a variety of cell lines cultured in vitro. When PGE1 responses were present, the effect was nearly maximal after a 5 min exposure and was well maintained for 60 min. Dose response curves for PGE1 were complex and also exhibited clonal variation. The relative potencies of prostaglandins were: PGE1 > PGE2 > PGA1. PGF(1α) and PGB1 were inactive at the concentration tested, indicating receptor specificity. When parental lines with no or small responses to PGE1 were fused to cells with larger responses to PGE1, the resulting hybrid cells expressed high levels of PGE1 responsiveness in the majority of cases. Clonal differences in potentiation by theophylline of peak PGE1 or catecholamine effects on intracellular cyclic AMP levels were also found. When theophylline sensitive cells were fused to theophylline insensitive cells, the resulting hybrids were responsive to theophylline. Thus, the inheritance of PGE and theophylline responses in somatic cell hybrids is distinctly different from that seen for β adrenergic responses, suggesting fundamental differences in their genetic regulation. These data could indicate different types of receptor mechanisms for catecholamines and prostaglandins.

Original languageEnglish (US)
Pages (from-to)6618-6625
Number of pages8
JournalJournal of Biological Chemistry
Volume248
Issue number19
StatePublished - 1973

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Hybrid Cells
Alprostadil
Theophylline
Metabolism
Cyclic AMP
Genes
Gene Expression
Adenosine
Catecholamine Receptors
Prostaglandin Receptors
Prostaglandins F
Prostaglandins E
Dinoprostone
Adrenergic Agents
Prostaglandins
Catecholamines
Cells
Cell Line

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. II. The effects of prostaglandin E1 and theophylline on parental and hybrid cells",
abstract = "Clonal differences in the response to prostaglandin E1 (PGE1) were found when changes in the intracellular concentration of cyclic adenosine 3':5' monophosphate (cyclic AMP) were measured following exposure to this agent in a variety of cell lines cultured in vitro. When PGE1 responses were present, the effect was nearly maximal after a 5 min exposure and was well maintained for 60 min. Dose response curves for PGE1 were complex and also exhibited clonal variation. The relative potencies of prostaglandins were: PGE1 > PGE2 > PGA1. PGF(1α) and PGB1 were inactive at the concentration tested, indicating receptor specificity. When parental lines with no or small responses to PGE1 were fused to cells with larger responses to PGE1, the resulting hybrid cells expressed high levels of PGE1 responsiveness in the majority of cases. Clonal differences in potentiation by theophylline of peak PGE1 or catecholamine effects on intracellular cyclic AMP levels were also found. When theophylline sensitive cells were fused to theophylline insensitive cells, the resulting hybrids were responsive to theophylline. Thus, the inheritance of PGE and theophylline responses in somatic cell hybrids is distinctly different from that seen for β adrenergic responses, suggesting fundamental differences in their genetic regulation. These data could indicate different types of receptor mechanisms for catecholamines and prostaglandins.",
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N2 - Clonal differences in the response to prostaglandin E1 (PGE1) were found when changes in the intracellular concentration of cyclic adenosine 3':5' monophosphate (cyclic AMP) were measured following exposure to this agent in a variety of cell lines cultured in vitro. When PGE1 responses were present, the effect was nearly maximal after a 5 min exposure and was well maintained for 60 min. Dose response curves for PGE1 were complex and also exhibited clonal variation. The relative potencies of prostaglandins were: PGE1 > PGE2 > PGA1. PGF(1α) and PGB1 were inactive at the concentration tested, indicating receptor specificity. When parental lines with no or small responses to PGE1 were fused to cells with larger responses to PGE1, the resulting hybrid cells expressed high levels of PGE1 responsiveness in the majority of cases. Clonal differences in potentiation by theophylline of peak PGE1 or catecholamine effects on intracellular cyclic AMP levels were also found. When theophylline sensitive cells were fused to theophylline insensitive cells, the resulting hybrids were responsive to theophylline. Thus, the inheritance of PGE and theophylline responses in somatic cell hybrids is distinctly different from that seen for β adrenergic responses, suggesting fundamental differences in their genetic regulation. These data could indicate different types of receptor mechanisms for catecholamines and prostaglandins.

AB - Clonal differences in the response to prostaglandin E1 (PGE1) were found when changes in the intracellular concentration of cyclic adenosine 3':5' monophosphate (cyclic AMP) were measured following exposure to this agent in a variety of cell lines cultured in vitro. When PGE1 responses were present, the effect was nearly maximal after a 5 min exposure and was well maintained for 60 min. Dose response curves for PGE1 were complex and also exhibited clonal variation. The relative potencies of prostaglandins were: PGE1 > PGE2 > PGA1. PGF(1α) and PGB1 were inactive at the concentration tested, indicating receptor specificity. When parental lines with no or small responses to PGE1 were fused to cells with larger responses to PGE1, the resulting hybrid cells expressed high levels of PGE1 responsiveness in the majority of cases. Clonal differences in potentiation by theophylline of peak PGE1 or catecholamine effects on intracellular cyclic AMP levels were also found. When theophylline sensitive cells were fused to theophylline insensitive cells, the resulting hybrids were responsive to theophylline. Thus, the inheritance of PGE and theophylline responses in somatic cell hybrids is distinctly different from that seen for β adrenergic responses, suggesting fundamental differences in their genetic regulation. These data could indicate different types of receptor mechanisms for catecholamines and prostaglandins.

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