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Bradykinin-stimulated phosphatidate and 1,2-diacylglycerol accumulation in guinea-pig airway smooth muscle: evidence for regulation 'down-stream' of phospholipases

Pyne, S and Pyne, N J (1994) Bradykinin-stimulated phosphatidate and 1,2-diacylglycerol accumulation in guinea-pig airway smooth muscle: evidence for regulation 'down-stream' of phospholipases. Cellular Signalling, 6 (3). pp. 269-77. ISSN 0898-6568

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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.

Item type: Article
ID code: 34917
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, Therapeutics. Pharmacology, Cell Biology
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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    Depositing user: Pure Administrator
    Date Deposited: 15 Nov 2011 05:18
    Last modified: 05 Sep 2014 12:32
    URI: http://strathprints.strath.ac.uk/id/eprint/34917

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