Bombesin enhancement of cAMP accumulation in swiss 3T3 cells: Evidence of a dual mechanism of action

Journal of Cellular Physiology - Tập 137 Số 2 - Trang 214-222 - 1988
Jonathan Millar1, Enrique Rozengurt2
1Imperial Cancer Research Fund, Lincoln's Inn Fields, United Kingdom.
2Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom

Tóm tắt

AbstractAddition of bombesin in the presence of either forskolin or cholera toxin caused a marked (4–6 fold) enhancement of cAMP accumulation in Swiss 3T3 cells. This effect was time and concentration dependent, induced by various bombesin‐like peptides and blocked by a bombesin antagonist. Enhancement of cAMP accumulation by bombesin was diminished by chronic pretreatment with phorbol dibutyrate implicating the involvement of protein kinase C in the activation. Pretreatment with pertussis toxin, which uncouples protein kinase C activation from cAMP accumulation (Proc. Natl. Acad. Sci. U.S.A., 84:2282, 1987) also inhibited bombesin enhancement of cAMP. Bombesin was also shown to release E type prostaglandins into the medium, an effect which was abolished by the cyclooxgenase inhibitor indomethacin. Low concentrations (100 nM) of indomethacin partially inhibited the accumulation of cAMP by bombesin in the presence of forskolin indicating that the release of E type prostaglandins into the medium is also involved in the accumulation of cAMP by bombesin. The additive nature of PBt2‐mediated down‐regulation and treatment with indomethacin suggests that activation of protein kinase C and the release of E type prostaglandins provide two distinct pathways involved in the enhancement of cAMP accumulation by bombesin. Finally, bombesin in the presence of forskolin stimulated the phosphorylation of the intermediate filament component vimentin, identified in the accompanying paper as a substrate for a cAMP dependent protein kinase in intact Swiss 3T3 cells.

Từ khóa


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Thông tin xuất bản

Journal of Cellular Physiology

Tập 137 Số 2

214-222

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