Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity |
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Authors: | A M Mamoon J Smith R C Baker J M Farley PhD |
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Institution: | (1) Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA |
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Abstract: | Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of 3H]phosphatidic acid (3H]PA) and 3H]phosphatidylethanol (3H]PEth) after labeling the muscle strips with 3H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both 3H]PA and 3H]PEth in a concentration-dependent manner (>105–400% vs. controls in the presence of 10–6 to 10–4
M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10–6
M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10–8 to 10–6
M) and GFX (10–8 to 10–6
M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle. |
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Keywords: | Phospholipase D Protein kinase C Acetylcholine Airway smooth muscle |
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