- 作者: A.M. Mamoon J. Smith R.C. Baker J.M. Farley
- 作者服務機構: Department of Pharmacology and Toxicology, University of Mississippi Mdeical Center, Jackson, Miss., USA
- 中文摘要: --
- 英文摘要: Phospholipase D(PLD) is a phosphodiesterase that cata-lyses hydrolysis of phosphatidylcholine to producephosphatidic acid and choline. In the presence of etha-nol, PLD also catalyses the formation of phosphatidyl-ethanol, which is a unique characteristic of this enzyme.Muscarinic receptor-induced changes in the activity ofPLD were investigated in porcine tracheal smooth mus-cle by measuring the formation of [ H] phosphatidic acid([3H]PA) and [3H]phosphatidylethanol([ H]PEth)after la-beling the muscle strips with [ H]palmitic acid. The cho-linergic receptor agonist acetylcholine (Ach)significantlybut transiently increased formation of both [ H]PA and[3H〕PEth in a concentration-dependent manner(>105-400% vs. controls in the presence of 10 to 10 MAch)when pretreated with 100 mMethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atro-pine(10 M), indicating that activation of PLD occurredvia muscarinic receptors. Activation of protein kinase C(PKC) by phorbol-12-myristate-13-acetate(PMA) in-creased PLD activity that was effectively blocked by thePKC inhibitors calphostin C(10 to 10 M) and GFX(10 to 10 M). Ach-induced increases in PLD activity werealso significantly, but incompletely, inhibited by bothGFX and calphostin C. From the present data, we con-clude that in tracheal smooth muscle, muscarinic acetyl-choline receptor-induced PLD activation is transient innature and coupled to these receptors via PKC. However,PKC activation is not solely responsible for Ach-inducedactivation of PLD in porcine tracheal smooth muscle.
- 中文關鍵字: --
- 英文關鍵字: Phospholipase D. Protein Kinase C. Acetylcholine. Airway smooth muscle