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Role of a pertussis toxin sensitive G-protein in mediating the effects of phorbol esters on receptor activated cyclic AMP accumulation in Jurkat cells

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Summary

In the human T -cell line, Jurkat, the accumulation of cyclic AMP induced by adenosine is enhanced by tumor-promoting phorbol esters, whereas prostaglandin E2 receptor-stimulated cAMP accumulation is antagonized (Nordstedt et al. 1989). In the present study we examine the involvement of pertussis toxin sensitive guanine nucleotide binding proteins (G-proteins) in producing the phorbol ester effects.

Pertussis toxin pretreatment of the Jurkat cells invariably caused an ADP ribosylation of two G-proteins that inhibit adenylyl cyclase, tentatively identified as Gi2 and Gi3, using Western blots. Pertussis toxin treatment had little effect on basal cAMP accumulation, but sometimes inhibited, sometimes stimulated agonist and cholera toxin induced cAMP accumulation. The latter effect was not mimicked by the B-oligomer. Irrespective of whether pertussis toxin stimulated or inhibited NECA and cholera toxin-induced cAMP accumulation it could not block the effect of phorbol-12,13-dibutyrate (PDBu). The inhibitory effect of PDBu on prostaglandin E2-induced cAMP accumulation was, however, invariably eliminated by pertussis toxin treatment.

In conclusion, activation of protein kinase C by phorbol esters reveals a Gi-mediated prostaglandin E receptor-induced inhibition of adenylate cyclase in addition to the prostaglandin E receptor-mediated stimulation of cAMP accumulation in Jurkat cells. The enhancement of adenosine A2 receptor stimulated CAMP accumulation by PDBu, on the other hand, does not involve a PTX sensitive Gi-protein.

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Author notes

  1. Christer Nordstedt

    Present address: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, 10021, New York, NY, USA

Authors and Affiliations

  1. Department of Pharmacology, Karolinska Institutet, Box 60400, S-104 01, Stockholm, Sweden

    Ingeborg van der Ploeg, Nedret Altiok, Anders Kvanta, Christer Nordstedt & Bertil B. Fredholm

  2. Department of Immunology, Karolinska Institutet, Box 60400, S-104 01, Stockholm, Sweden

    Anders Kvanta

Authors
  1. Ingeborg van der Ploeg
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  2. Nedret Altiok
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  3. Anders Kvanta
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  4. Christer Nordstedt
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  5. Bertil B. Fredholm
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van der Ploeg, I., Altiok, N., Kvanta, A. et al. Role of a pertussis toxin sensitive G-protein in mediating the effects of phorbol esters on receptor activated cyclic AMP accumulation in Jurkat cells. Naunyn-Schmiedeberg's Arch Pharmacol 344, 611–617 (1991). https://doi.org/10.1007/BF00170660

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  • DOI: https://doi.org/10.1007/BF00170660

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