Ca2+-channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle cells.

Block, Lutz H.; Emmons, Lyman R.; Vogt, Esther; Sachinidis, Agapios; Vetter, W; Hoppe, Jürgen

doi:10.1073/pnas.86.7.2388

Cited by 123 publications

(58 citation statements)

References 29 publications

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“…It is possible that the calcium channel blockers could interfere with the binding of the mitogens to their receptors on the cell, or that they might be uncoupling receptor activation from signal transduction pathways within the membrane, as suggested by Block et al 7 Evidence for these mechanisms comes from their studies with vascular smooth muscle cells, in which they found that calcium channel blockers not only inhibited PDGF-induced mitogenesis but also PDGF-induced vasoconstriction. They demonstrated that the three calcium channel blockers verapamil, nifedipine, and diltiazem all prevented the increases in cytosolic calcium, phosphoinositide turnover, and production of diacylglycerol induced by PDGF-BB and that the first two calcium channel blockers also prevented translocation of protein kinase C to the plasma membrane induced by PDGF-AA.…”

Section: Methodsmentioning

confidence: 95%

Inhibition of human mesangial cell proliferation by calcium channel blockers.

Shultz

Raij

1990

Hypertension

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Human mesangial cells in culture proliferate in response to platelet-derived growth factor (PDGF) and thrombin. Both of these agents also induce changes in cytosolic calcium that are dependent on both mobilization of intracellular calcium and influx of extracellular calcium. We hypothesized that calcium channel blockers, by preventing influx of extracellular calcium, may inhibit proliferation induced by these mitogens. We found that three different calcium channel blockers, diltiazem, nifediplne, and verapamil, were able to significantly inhibit [

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Section: Methodsmentioning

confidence: 95%

Inhibition of human mesangial cell proliferation by calcium channel blockers.

Shultz

Raij

1990

Hypertension

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“…2). This rapid and protracted redistribution of PKC in response to phorbol esters has been described in a variety of cell types [24][25][26][27]30,31].…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C translocation in intact vascular smooth muscle strips

Haller

Smallwood

Rasmussen

1990

Biochemical Journal

108

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Using intact muscle strips from the bovine carotid artery, the time course of translc~ation of protein kinase C (PKC) from the cytosol to the membrane fraction was measured in response to various agonists at induce contractile responses. PKC activity was assessed by Ca2+/phospholipid-dependent phosphorylation of histoiie. Exposure of the muscle strips to phorbol ester (12-deoxyphorbol 1 3-isobutyrate) induced a rapid and sustained translocation of PKC from the cytosol to the membrane fraction, and a slowly developing but sustained contractile response. Histamine induced a comparable initial translocation of PKC to the membrane which then decreased somewhat to a stable plateau significantly above basal values. Histamine also led to a rapid and sustained increase in tension. Angiotensin I, which caused a rapid but transient contraction, induced a rapid initial translocation of PKC to the membrane. The men. brane-associated PKC then declined to a stable plateau significantly lower than that seen after a histamine-induced respon.e, and only slightly above the basal value. Endothelin, which induced a sustained contraction, caused a sustained translocation of PKC from the cytosol to the membrane. In contrast, although exposure to 35 mM-KCI induced a rapid and sustained contraction, it caused only a transient translocation of PKC; the membrane-associated PKC returned to its basal value within 20 min. These results demonstrate that PKC in intact smooth muscle can be rapidly translocated to the membrane and remains membranebound during sustained phorbol ester-or agonist-induced contractions, but that such .t sustained translocation of PKC does not occur during prolonged stimulation with KCI. INTRODUCTIONThe Ca2+/phospholipid-dependent protein kinase, protein kinase C (PKC), is widely distributed in tissues and organs [1]. Over the last few years the enzyme has been implicated in the regulation of an increasing number of cellular processes [1][2][3][4]. In vascular smooth muscle, PKC is present in relatively high concentrations [4], suggesting that it also plays an important role in the control of smooth muscle function. A unique feature of PKC regulation is the spatial translocation of the enzyme. Under basal conditions PKC is thought to be located mainly in the cytosol, but after hormonal stimulation PKC is rapidly translocated to the membrane where it associates with membrane phospholipids [4]. The activation of the enzyme is often closely linked to changes in phosphoinositide (PI) metabolism [3]. When an appropriate agonist activates a specific receptor, an immediate receptor-linked event is the activation of a specific phospholipase C that catalyses the rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to two intracellular messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) [2]. It has been shown that IP3 triggers the release of Ca2+ from intracellular stores in smooth-muscle [5]. Likewise, it has been demonstrated that appropriate agonists induce sustained increases in the DAG cont...

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“…First, the increased A-chain expression may be associated with an incomplete stimulation of cell growth (34). Interestingly, a glioma-derived PDGF A-chain homodimer may be less potent than either the A-B heterodimer or the B-chain homodimer in its mitogenic activity and its ability to stimulate receptor autophosphorylation (35). Recently, a transmembrane tyrosine kinase has been isolated that efficiently binds PDGF A-chain homodimers but is structurally distinct from the PDGF B-type receptor (36).…”

Section: Discussionmentioning

confidence: 99%

Increased platelet-derived growth factor A-chain expression in human uterine smooth muscle cells during the physiologic hypertrophy of pregnancy.

Mendoza

Young

Orkin

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Platelet-derived growth factor (PDGF) has been implicated in the cell proliferation and directed cell movement in various physiologic and pathologic processes. To explore the role of PDGF in a reversible physiologic process, adaptation of the uterus to pregnancy, expression of PDGF in tissue sections of human gestational myometrium was demonstrated by immunohistochemical techniques and confirmed by nuclease protection analysis. Commensurate with an increase in immunoreactive PDGF expression in the myometrial smooth muscle cells, increased levels of PDGF A-chain mRNA, but not PDGF B-chain or PDGF B-type receptor transcripts, were seen in the gravid uterus relative to the nongravid uterus. The amount of A-chain transcript increased during gestation and diminished during the puerperium. These observations demonstrate PDGF polypeptide expression in situ and implicate PDGF in a normal physiologic process-uterine expansion during pregnancy.Platelet-derived growth factor (PDGF) is a growth factor which is mitogenic and chemotactic for smooth muscle cells and fibroblasts (1-3). PDGF is a dimer of two chains, designated A and B, that acts upon cells by binding to specific cell-surface receptors. All three dimeric isotypes of PDGF, PDGF-AA, -AB, and -BB, have been shown to be biologically active (4-7). The A and B chains of PDGF are the products of separate but related genes. The B chain is the product of the c-sis gene and is located on chromosome 22 (8-10). The homologous A-chain gene is found on chromosome 7 (11). Unlike the B-chain gene (12-16), two different A-chain precursors can be generated from the A-chain gene as a result of alternative splicing events that include or exclude the 69-base-pair (bp) sixth exon of the A-chain gene (17,18 (30 min). Each incubation was followed by a wash with buffered saline and a 15-min incubation with 0.5 M Tris HCl (pH 7.4) supplemented with 1% goat serum. Antibody localization was effected by a 5-min incubation with a freshly prepared solution of0.0006% 3,3-diaminobenzidine tetrahydrochloride in 0.1 M Tris HCI (pH 7.4) supplemented with 1% goat serum and 0.0003% hydrogen peroxide. After washing in tap water, the sections were counterstained with hematoxylin.RNA Isolation. Total RNA was prepared by the guanidine isothiocyanate/CsCl method (23). Briefly, the tissue was disrupted in 4 M guanidine isothiocyanate using a tissue homogenizer (Tekmar, Cinncinati) and the lysate was layered onto 5.7 M CsCl. After ultracentrifugation, the RNA pellet was harvested, phenol extracted, and ethanol precipitated. The concentration of RNA was determined from the absorbance at 260 nm. Seven and one-halfmicrograms ofRNA was dissolved in 12 Al [50%o formamide/5% formaldehyde/40 mM morpholinepropane sulfonic acid (Mops)/10 mM sodium acetate/1 mM EDTA, pH 7.0], heated for 15 min at 68°C, and size fractionated by electrophoresis on 1% agarose gels containing 5% formaldehyde in 40 mM Mops/10 mM sodium acetate/1 mM EDTA. Following electrophoresis, the gels were rinsed in distilled water, stain...

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Ca2+-channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle cells.

Cited by 123 publications

References 29 publications

Inhibition of human mesangial cell proliferation by calcium channel blockers.

Inhibition of human mesangial cell proliferation by calcium channel blockers.

Protein kinase C translocation in intact vascular smooth muscle strips

Increased platelet-derived growth factor A-chain expression in human uterine smooth muscle cells during the physiologic hypertrophy of pregnancy.

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