Modulation of prolactin-stimulated nb2lymphoma cell mitogenesis by cholera toxin and pertussis toxin

Jennifer Lynn Larsen, Maria L. Dufau

Research output: Contribution to journalArticle

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Abstract

We have investigated whether cholera toxin (CT)- or pertussis toxin (IAP)-sensitive G proteins are involved in ovine (o) PRL-stimulated mitogenesis in the lactogen-dependent rat Nb2 node lymphoma cell line. Addition of IAP to medium caused a biphasic effect on oPRL-stimulated cell number. Low doses (10-3ng/ml) enhanced (mean ± SEM, 15 ± 3%) whereas higher doses (â�« 10 ng/ml) inhibited (24 ± 3%) mitogenesis stimulated by a submaximal dose of oPRL (0.1 ng/ml) compared to control values. The cAMP analog 8-bromo-cAMP also had a biphasic effect on cell division stimulated by submaximal doses of PRL. Low doses (10-5M) enhanced whereas higher doses (10-3M) inhibited Nb2 cell growth in response to PRL. Incubation with CT only inhibited oPRL-stimulated mitogenesis in a dose-dependent manner. Maximal inhibition (63 ± 7%) occurred at a concentration of 10 ng/ml or more. Phorbol myristate acetate (PMA) enhanced mitogenesis stimulated by PRL alone and in the presence of either stimulatory or inhibitory doses of IAP, but PMA did not block IAP inhibition. In contrast, PMA had no effect on cells incubated with CT; the inhibition of PRL-stimulated cell division by CT remained unchanged. Lactogenic receptor-binding sites per cell and affinity were not significantly affected by PMA, IAP, or CT, suggesting a postreceptor mechanism of action.In summary, these data demonstrate that cAMP modifies PRL-stimulated Nb2 cell mitogenesis. The differences between IAP and CT (i.e. biphasic effect, degree of inhibition, and differential effect of PMA) suggest that these agents could also modulate PRL actions in the Nb2cell through different mechanisms, including a cAMP-independent pathway.

Original languageEnglish (US)
Pages (from-to)438-444
Number of pages7
JournalEndocrinology
Volume123
Issue number1
DOIs
StatePublished - Jul 1 1988

Fingerprint

Cholera Toxin
Pertussis Toxin
Prolactin
Tetradecanoylphorbol Acetate
Cell Division
8-Bromo Cyclic Adenosine Monophosphate
GTP-Binding Proteins
Lymphoma
Sheep
Cell Count
Binding Sites
Cell Line
Growth

ASJC Scopus subject areas

  • Endocrinology

Cite this

Modulation of prolactin-stimulated nb2lymphoma cell mitogenesis by cholera toxin and pertussis toxin. / Larsen, Jennifer Lynn; Dufau, Maria L.

In: Endocrinology, Vol. 123, No. 1, 01.07.1988, p. 438-444.

Research output: Contribution to journalArticle

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abstract = "We have investigated whether cholera toxin (CT)- or pertussis toxin (IAP)-sensitive G proteins are involved in ovine (o) PRL-stimulated mitogenesis in the lactogen-dependent rat Nb2 node lymphoma cell line. Addition of IAP to medium caused a biphasic effect on oPRL-stimulated cell number. Low doses (10-3ng/ml) enhanced (mean ± SEM, 15 ± 3{\%}) whereas higher doses ({\^a}�« 10 ng/ml) inhibited (24 ± 3{\%}) mitogenesis stimulated by a submaximal dose of oPRL (0.1 ng/ml) compared to control values. The cAMP analog 8-bromo-cAMP also had a biphasic effect on cell division stimulated by submaximal doses of PRL. Low doses (10-5M) enhanced whereas higher doses (10-3M) inhibited Nb2 cell growth in response to PRL. Incubation with CT only inhibited oPRL-stimulated mitogenesis in a dose-dependent manner. Maximal inhibition (63 ± 7{\%}) occurred at a concentration of 10 ng/ml or more. Phorbol myristate acetate (PMA) enhanced mitogenesis stimulated by PRL alone and in the presence of either stimulatory or inhibitory doses of IAP, but PMA did not block IAP inhibition. In contrast, PMA had no effect on cells incubated with CT; the inhibition of PRL-stimulated cell division by CT remained unchanged. Lactogenic receptor-binding sites per cell and affinity were not significantly affected by PMA, IAP, or CT, suggesting a postreceptor mechanism of action.In summary, these data demonstrate that cAMP modifies PRL-stimulated Nb2 cell mitogenesis. The differences between IAP and CT (i.e. biphasic effect, degree of inhibition, and differential effect of PMA) suggest that these agents could also modulate PRL actions in the Nb2cell through different mechanisms, including a cAMP-independent pathway.",
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