Interference of phorbolesters with endothelium-dependent vascular smooth muscle relaxation

Weinheimer, G.; Wagner, Bernd; Oßwald, Hartmut

doi:10.1016/0014-2999(86)90285-2

Cited by 43 publications

(12 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another intracellular messenger has been implicated in the control of EDRF release by the demonstration that phorbol esters can inhibit EDRF release from intact rings of guineapig pulmonary artery (Weinheimer et al, 1986) or rabbit aorta (Lewis & Henderson, 1987) and from bovine cultured aortic 1 Author for correspondence. endothelial cells in a bioassay system (de Nucci et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…The study of de Nucci et al (1988) used only a single concentration of phorbol ester, and did not examine the time course of the effects of the phorbol ester. The study of Weinheimer et al (1986) used a range of phorbol ester concentrations, but again did not examine the time course of the effects of the phorbol ester. Martin et al (1988) demonstrated that cultured aortic endothelial cells of the pig respond to the EDRF they produce with an increase in cyclic GMP levels.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Release of endothelium‐derived relaxing factor from pig cultured aortic endothelial cells, as assessed by changes in endothelial cell cyclic GMP content, is inhibited by a phorbol ester

Smith

Lang

1990

British J Pharmacology

View full text Add to dashboard Cite

Cultured aortic endothelial cells of the pig respond to the endothelium‐derived relaxing factor (EDRF) they release with an increase in cyclic GMP content. This response is inhibited by haemoglobin or by l‐NG‐monomethyl‐arginine (l‐NMMA), and has been used to investigate the effects of phorbol esters on EDRF release. Pretreatment with phorbol‐12,13‐dibutyrate (PDB) but not the inactive 4α‐phorbol‐12,13,‐didecanoate (PDD), inhibited increases in cyclic GMP induced by substance P (10−8 m) in a time and concentration‐dependent manner. PDB did not affect basal cyclic GMP levels. PDB (3 × 10−7 m), but not PDD (3 × 10−7 m), also inhibited ATP (10−5 m)‐induced increases in cyclic GMP, but did not affect those induced by bradykinin (10−7 m). Increases in cyclic GMP induced by low (10−7 m) but not high (10−6 m) concentrations of the calcium ionophore A23187 were inhibited by PDB (3 × 10−7 m). This inhibitory effect was due to enhanced destruction of EDRF by superoxide anions rather than inhibition of EDRF release, as the inhibition was abolished in the presence of superoxide dismutase (SOD, 30 u ml−1) and catalase (CAT, 100 u ml−1). SOD and CAT did not affect the inhibitory action of PDB on substance P or ATP‐induced increases in cyclic GMP. Increases in endothelial cell cyclic GMP content induced by sodium nitroprusside (10−5 m) were unaffected by PDB pretreatment. The inhibitory effects of PDB are probably a result of an action of protein kinase C on the steps between receptor occupation and phospholipase C activation.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Release of endothelium‐derived relaxing factor from pig cultured aortic endothelial cells, as assessed by changes in endothelial cell cyclic GMP content, is inhibited by a phorbol ester

Smith

Lang

1990

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Recently, attempts have been made to determine if other intracellular second messenger systems such as protein kinase C and the cyclic nucleotides modulate calcium mobilisation in the vascular endothelium. For example, tumour-promoting phorbol esters, which activate protein kinase C (Castagna et al, 1982) inhibit endothelium-dependent relaxation induced by histamine in guinea-pig pulmonary artery (Weinheimer et al, 1986), acetylcholine and substance P in rabbit aorta (Lewis & Henderson, 1987) and acetylcholine in rabbit pulmonary artery (Cherry & Gillis, 1988). The inability of phorbol esters to inhibit relaxations induced by sodium nitroprusside (Lewis & Henderson, 1987) suggests that these compounds inhibit the production, but not the action, of EDRF.…”

Section: Introductionmentioning

confidence: 99%

Modulation of agonist‐induced calcium mobilisation in bovine aortic endothelial cells by phorbol myristate acetate and cyclic AMP but not cyclic GMP

Buchan

Martin

1991

British J Pharmacology

View full text Add to dashboard Cite

1 In bovine aortic endothelial cells (BAEC), thrombin (1 u ml-'), bradykinin (1-10 nM) and adenosine triphosphate (ATP) (0.3 pM-100uM) each induced a biphasic elevation of cytosolic calcium ([Ca2"],), con-sisting of an initial transient followed by a sustained plateau phase. 6 NG nitro-L-arginine (50,pM), an inhibitor of nitric oxide synthase, had no effect on the magnitude of the initial transient elevation of [Ca21]i induced by thrombin (1 uml-), bradykinin (1 nM) or ATP (3,pM), and had no effect on the plateau phase of the increase in [Ca2+]i induced by these agents.7 These findings suggest that while activation of protein kinase C inhibits and elevation of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) augments calcium mobilisation in bovine aortic endothelial cells, elevation of cyclic GMP appears to have no effect.

show abstract

“…Since the relaxation was abolished almost completely by removal of the endothelium, A23187 does not seem to act directly on smooth muscle cells. A23187 also produces relaxations that depend on the endothelium in rabbit aortas 25 -27 and in guinea pig pulmonary 28 and human coronary 2930 arteries. The relaxation induced by A23187 in isolated dog basilar arteries is not affected by indomethacin.…”

mentioning

confidence: 99%

Endothelium-dependent and -independent responses to vasodilators of isolated dog cerebral arteries.

Onoue

Nakamura

Toda

1988

Stroke

View full text Add to dashboard Cite

We compared responses to calcium ionophore A23187, vasopressin, and substance P in helical strips of dog middle cerebral, basilar, and posterior communicating arteries to obtain a better understanding of humoral control of cerebrovascular tone in different brain regions and its potential impact on mechanisms of cerebral vasospasm. A23187 relaxed these different arterial strips partially precontracted with prostaglandin F 2a to a similar extent. Vasopressin produced concentration-dependent relaxation in basilar and posterior communicating arterial strips, whereas middle cerebral arterial strips either contracted or relaxed slightly. Relaxations induced by A23187 and vasopressin were either abolished or converted to contractions by removal of the endothelium. In contrast, the relaxation of cerebral arterial strips to substance P was markedly attenuated but not abolished by endothelium denudation; the remaining relaxation was suppressed by indomethacin. In some cerebral arterial strips with intact endothelium, substance P caused a transient contraction that was reversed to a relaxation by indomethacin or ONO-3708, a prostaglandin antagonist. In arterial strips denuded of endothelium from the same dogs, substance P always produced relaxations. Relaxations of cerebral arterial strips to A23187 and vasopressin appear to be mediated by endothelium-derived relaxing factor. The function of vasopressin receptors in endothelial cells differs markedly in basilar and posterior communicating arteries versus middle cerebral arteries. Substance P-induced relaxations appear to be primarily associated with endothelium-derived relaxing factor and with prostaglandin I 2 , whereas contractions appear to be mediated by endotheliumderived prostaglandins. (Stroke 1988;19:1388-1394)

show abstract

Interference of phorbolesters with endothelium-dependent vascular smooth muscle relaxation

Cited by 43 publications

References 8 publications

Release of endothelium‐derived relaxing factor from pig cultured aortic endothelial cells, as assessed by changes in endothelial cell cyclic GMP content, is inhibited by a phorbol ester

Release of endothelium‐derived relaxing factor from pig cultured aortic endothelial cells, as assessed by changes in endothelial cell cyclic GMP content, is inhibited by a phorbol ester

Modulation of agonist‐induced calcium mobilisation in bovine aortic endothelial cells by phorbol myristate acetate and cyclic AMP but not cyclic GMP

Endothelium-dependent and -independent responses to vasodilators of isolated dog cerebral arteries.

Contact Info

Product

Resources

About