Phorbol ester-induced contraction of arterial smooth muscle and inhibition of α-adrenergic response

Danthuluri, N. Raju; Deth, Richard C.

doi:10.1016/0006-291x(84)91397-4

Cited by 209 publications

(68 citation statements)

References 17 publications

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“…This thesis has been supported by numerous succeeding reports, using a variety of arterial smooth muscles (Danthuluri and Deth, 1984; Bara van et ai. , 1985; Forder et ai.…”

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confidence: 55%

“…To explain the force main tenance during the sustained phase of smooth mus cle contraction, the occurrence of a "latch mechanism" in the myosin-actin interaction has been proposed (Aksoy et aI., 1982(Aksoy et aI., , 1983, In keep ing with this line of thinking, Rasmussen et al (1987) advocated that the sustained smooth muscle contraction is due to phosphorylation of proteins other than myosin light chain by protein kinase C (PKC). This thesis has been supported by numerous succeeding reports, using a variety of arterial smooth muscles (Danthuluri and Deth, 1984;Bara van et ai. , 1985;Forder et ai.…”

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confidence: 55%

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Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Matsui¹,

Takuwa

Johshita³

et al. 1991

J Cereb Blood Flow Metab

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Summary:In the present study, we investigate the pos sible role of protein kinase C (PKC)-dependent smooth muscle contraction in cerebral vasospasm following sub arachnoid hemorrhage (SAH), employing the beagle "two-hemorrhage" model. The occurrence of chronic va sospasm was angiographically confirmed on day 7 in the basilar artery, which was exposed via the transclival ap proach. The artery was superfused with aerated Krebs Henseleit solution containing various agents, and the sub sequent changes in the basilar artery diameter were re corded by successive angiography. The preexisting spasm was not ameliorated by local application of neuro transmitter antagonists (atropine, methysergide, phentol amine, and diphenhydramine), calmodulin inhibitors (R24571 and W-7), or a calcium antagonist, nicardipine. However, the application of PKC inhibitors such as H-7 and staurosporine induced significant dilation of the ar tery. In another experiment, an intrinsic PKC activator,The refractoriness of chronic vasospasm to va sodilator therapy has been well documented (Bevan and Bevan, 1988). Particularly, the Ca2+ -antagonist nimodipine, administered via various routes, has in variably failed to reverse chronic vasospasm (Espi nosa et aI. , 1984; Grotenhuis et aI., 1984; Nosko et aI., 1985; Lewis et aI., 1988). Since agonist-induced smooth muscle contraction has been thought to be dependent on intracellular influx of external Ca2+, Received December 28, 1989; revised July 23, 1990; accepted July 24, 1990. 1431,2-diacylglycerol (DAG), in the basilar artery, the CSF, and the cisternal clot of beagles exposed to two hemor rhages was measured on days 1, 2,4,7, and 14 using the DAG kinase method. On days 2, 4, and 7, the DAG con tent of the basilar artery showed a significant and pro longed increase (150-190% of control), whereas it was unchanged on days I and 14. Throughout the experimen tal period, there was a significant linear correlation be tween the DAG content and the angiographical diameter of the basilar artery. The above results indicate that SAH leads to an increase in the DAG level within the cerebral artery through an as yet unknown mechanism and that subsequent activation of the PKC-dependent contractile system participates in the occurrence of chronic vaso spasm. Key Words: Cerebral vasospasm-l,2-Diac ylglycerol-H-7-Protein kinase C-Vascular smooth muscle.it has been conjectured that the primary cause of chronic vasospasm might be the changes in the physical properties in the arterial wall rather than active smooth muscle contraction (Bevan and Be van, 1988; Findlay et aI., 1989; Kim et aI., 1989).However, it has recently been shown that during the sustained phase of agonist-induced smooth mus cle contraction, neither the intracellular concentra tion of Ca2+ nor the phosphorylation of myosin light chain is increased (DeFeo and Morgan, 1985;Kamm and Stull, 1985). To explain the force main tenance during the sustained phase of smooth mus cle contraction, the occurrence of a "latch mechanism" in the myosin-actin i...

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“…This thesis has been supported by numerous succeeding reports, using a variety of arterial smooth muscles (Danthuluri and Deth, 1984; Bara van et ai. , 1985; Forder et ai.…”

mentioning

confidence: 55%

mentioning

confidence: 55%

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Matsui¹,

Takuwa

Johshita³

et al. 1991

J Cereb Blood Flow Metab

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“…Support for this assumption comes from contraction studied with phorbol esters, activators of PKC [11]. Exposure of smooth muscle strips to phorbol ester leads to a slowly developing contraction which lasts for several hours [12][13][14]. It has also been shown that phorbol esters induce a sustained contraction in chemically skinned vascular smooth muscle when the Ca2+ concentration is maintained at 100 nM [15].…”

Section: Introductionmentioning

confidence: 99%

“…The phosphorylation of these proteins appears to occur as a direct or indirect consequence of the activation of PKC [17]. The temporal change in the pattern of phosphoproteins and the distinct effects ofphorbol esters on smooth muscle contraction [12][13][14] have led to the proposal that the initial and sustained phases of smooth muscle contraction are mediated by different cellular and molecular events [17]. In this model, the initial phase is characterized by an increase in the cytosolic Ca2+ concentration, the activation of the calmodulin-dependent myosin-light-chain kinase, the phosphorylation of the myosin light chains, an interaction of actin and myosin, and hence contraction.…”

Section: Introductionmentioning

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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“…Some evidence for such a mechanism has been advanced because phorbol esters, which activate protein kinase C with some selectivity (Blumberg et al, 1984;Nishizuka, 1984;Wolf et al, 1985), contract smooth muscle directly (Danthuluri & Deth, 1984;Rasmussen et al, 1984;Baraban et al, 1985;Dale & Obianime, 1985;Forder et al, 1985;Gleason & Flaim, 1986;Menkes et al, 1986;Miller et al, 1986;Sybertz et al, 1986) although inhibitory effects have also been reported (Baraban et al, 1985;Menkes et al, 1986). Phorbol esters also increase responsiveness to Ca2" channel activators, such as Bay K 8644 (Forder et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Interaction of phorbol esters with Ca²⁺ channels in smooth muscle

Spedding¹

1987

British J Pharmacology

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1 The phorbol ester 12-0-tetradecanoyl phorbol-1 3-acetate (TPA), a selective activator of protein kinase C, had no effect on the sensitivity to Ca2+ or verapamil of K+-depolarized taenia preparations from the guinea-pig caecum, despite the use of high concentrations (1 gM for 3 h); this preparation is sensitive to Ca2+ channel activators and antagonists. 2 TPA (0.03-33 M) caused a slow contraction of rat aorta preparations; the contractions were resistant to the calcium-antagonists nifedipine (0.01 M), verapamil (10 JM), diltiazem (1O gM) and cinnarizine (10 I1M), but were antagonized by N-(6-aminohexyl)-5-chloro -1-naphthalensulphonamide . Prolonged exposure to TPA (> 2 h) resulted in spontaneous contractions which were sensitive to verapamil (1 I1M). 3 Isoprenaline and sodium nitroprusside relaxed phenylephrine-induced contractions in rat aorta preparations. TPA (0.3 JM) blocked the maximal response to isoprenaline but not to sodium nitroprusside indicating that TPA did selectively activate protein kinase C under these experimental conditions. 4 These findings indicate that protein kinase C activation does not result in direct effects on Ca2+ channel function, but may exert effects indirectly (e.g. by modifying intracellular sensitivity to Ca2+, Ca2+ extrusion, or cellular depolarization).

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Phorbol ester-induced contraction of arterial smooth muscle and inhibition of α-adrenergic response

Cited by 209 publications

References 17 publications

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Protein kinase C translocation in intact vascular smooth muscle strips

Interaction of phorbol esters with Ca²⁺ channels in smooth muscle

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Phorbol ester-induced contraction of arterial smooth muscle and inhibition of α-adrenergic response

Cited by 209 publications

References 17 publications

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Protein kinase C translocation in intact vascular smooth muscle strips

Interaction of phorbol esters with Ca2+ channels in smooth muscle

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Interaction of phorbol esters with Ca²⁺ channels in smooth muscle