Endothelin‐1 stimulated phospholipase D in A10 vascular smooth muscle derived cells is dependent on tyrosine kinase Evidence for involvement in stimulation of mitogenesis

Abstract

The mechanism whereby endothelin stimulates motogenesis of vascular smooth muscle cells is not understood. Here we show that endothelin-1 stimulates phospholipase D by a protein kinase C and tyrosine kinase dependent mechanism, and present evidence that implicate the phosphatidic acid formed by phospholipase D in the mitogenic response.

Diacylglycerol metabolism in SM-3 smooth muscle cells

“…Although A10 cells have been used extensively for signal transduction research (Grillone et al 1988;Plevin and Wakelam 1992;Welsh et al 1990; Wilkes et al 1993), they lack many of the essential biochemical characteristics of vascular smooth muscle cells, such as calponin expression (Winder and Walsh 1996), because of phenotypic modulation from a contractile state to a synthetic state (Chamley-Campbell et al 1979). Therefore, caution must be exercised in the extrapolation of results on the metabolic fate of DG in noncontractile A10 cells (Chuang et al 1990(Chuang et al , 1993Migas and Severson 1996) to the physiological situation where contractility of smooth muscle cells is regulated to control vascular resistance and blood pressure.…”

The roles of multiple pathways in regulating bombesin-stimulated phospholipase D activity in Swiss 3T3 fibroblasts

“…Furthermore, the (PtdCho) to generate choline and phosphatidic acid (PtdOH) stimulation of PLD activity through cytosolic tyrosine kinases [1,2]. The peptide is a mitogen for Swiss 3T3 cells [3], binds to a has been reported in cells such as N-formylmethionyl-leucylsingle class of high-affinity cell-surface receptors [4] and also phenylalanine-stimulated neutrophils [10] and endothelinstimulates phospholipase C (PLC)-mediated Ptdlns(4,5)P2 hystimulated A10 vascular-smooth-muscle cells [11]. drolysis generating the second-messenger molecules Ins(1,4,5)P3…”

Endothelin Stimulates Phospholipase D in Striatal Astrocytes

“…In CNS, ET-l and ET-3 can be synthesized in neurons (Fuxe et al, 1991;Krsmanovic et al, 1991;Lysko et al, 1991), glial (MacCumber et al, 1990Hösli and Hösli, 1991), and endothelial (Vigne et al, 1990;Yoshimoto et al, 1990) cells, and all these cells exhibit high-affinity binding sites for these peptides. In glial cells, ET can act as a growth factor stimulating DNA synthesis In peripheral tissues, such as vascular smooth muscle cells (Wikles et al, 1993), iris sphincter smooth muscles (Zhang and Abdel-Latif, 1992), osteoblast cells (Suzuki et al, 1994), mesangial cells (Kester et a!., 1992), aorta (Liu et al, 1992), and fibroblasts (MacNulty et al, 1990), ET can also stimulate phospholipase D (PLD). Such an effect appears to occur as well in CNS (Ambar and Sokolovsky, 1993;Sarri et a!., 1995).…”