Abstract
Bradykinin-treatment of cultured airway smooth muscle (ASM) induced the formation of [3H]1,2-diacylglycerol ([3H]1,2-DG), [3H]1,3-diacylglycerol ([3H]1,3-DG) and [3H]phosphatidic acid ([3H]PtdOH) in [3H]palmitate-labelled cells and of [3H]choline in [3H]methyl choline-labelled cells. [3H]1,2-DG and [3H]1,3-DG responses were biphasic with an initial transient phase from 0-2 min and a second sustained phase to 10 min. In contrast, [3H]PtdOH accumulation plateaued at 2 min stimulation as did [3H]choline formation. The bradykinin-stimulated [3H]1,2-DG and [3H]PtdOH responses exhibited similar concentration dependencies (EC50 values: [3H]1,2-DG 5.14 +/- 2.82 nM; [3H]1,3-DG 4.95 +/- 1.12 nM; [3H]PtdOH 1.52 +/- 0.82 nM). In contrast, PMA elicited a [3H]PtdOH response, but was without effect upon [3H]DG levels. Bradykinin-induced accumulation of [3H]1,2-DG and [3H]PtdOH was insensitive to blockade by a bradykinin B2-receptor antagonist, NPC567 (40 microM) and the B1-receptor agonist, Des-Arg9-bradykinin, (10 microM) failed to elicit a response. These observations are similar to those obtained previously for bradykinin-stimulated phospholipase D activity in ASM (Pyne S. and Pyne N. J., Br. J. Pharmac. 110, 477-481, 1993). Thus, both bradykinin-stimulated 1,2-DG and PtdOH accumulation may also be regulated via a novel B3-receptor. Bradykinin-stimulated formation of [3H]PtdOH was partially inhibited by butan-1-ol (by 47.25 +/- 12.7%, n = 3) which had no effect upon basal or bradykinin-stimulated levels of [3H]1,2-DG or upon basal [3H]PtdOH.
Original language | English |
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Pages (from-to) | 269-77 |
Number of pages | 9 |
Journal | Cellular Signalling |
Volume | 6 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1994 |
Keywords
- bradykinin
- butanols
- cells
- choline
- diglycerides
- down-regulation
- muscle
- phosphatidic acids
- phospholipase D
- protein kinase C
- receptors
- signal transduction
- tetradecanoylphorbol acetate
- trachea
- type C phospholipases