Role of tyrosine phosphorylation in excitation–contraction coupling in vascular smooth muscle

Hughes, Alun D.; Wijetunge, S

doi:10.1046/j.1365-201x.1998.00446.x

Cited by 43 publications

(42 citation statements)

References 132 publications

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“…16 Tyrosine kinases have been shown to influence vascular contraction in large arteries and cultured myocytes from these vessels. 17,18 Moreover, we recently reported that renal arteriolar contractile responses to Ang II are suppressed by inhibition of EGFR tyrosine kinase activity. 8 The present study explored the …”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca ²⁺ Influx in Afferent Arterioles

Che¹,

Carmines²

2002

Hypertension

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Abstract-We previously reported that inhibition of epidermal growth factor receptor tyrosine kinase activity attenuates renal arteriolar contractile responses to angiotensin II. We performed the present experiments to determine if epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca 2ϩ ] response to angiotensin II. Afferent arterioles were dissected from rat kidney and intracellular [Ca 2ϩ ] was monitored with the use of fura-2. In normal Ringer's bath containing 1.5 mmol/L Ca 2ϩ , basal intracellular [Ca 2ϩ ] averaged 95Ϯ7 nmol/L and 100 nmol/L angiotensin II caused a rapid rise (peak ⌬ϭ75Ϯ10 nmol/L) that waned to a plateau averaging 24Ϯ5 nmol/L above baseline. Pretreatment with 100 nmol/L AG1478 (epidermal growth factor receptor tyrosine kinase inhibitor) reduced both the peak and the plateau stages of the angiotensin II response (peak ⌬ϭ42Ϯ7 nmol/L; plateau ⌬ϭ8Ϯ4 nmol/L). A structurally unrelated epidermal growth factor receptor tyrosine kinase inhibitor also suppressed the peak response to angiotensin II, whereas tyrosine phosphatase inhibition enhanced the plateau phase of the response. In the presence of 100 nmol/L extracellular Ca 2ϩ , the angiotensin II response was characterized by a peak of diminished magnitude (⌬ϭ49Ϯ10 nmol/L; PϽ0.05 versus the response in normal Ringer's bath) with no plateau, and this response was unaffected by AG1478. Moreover, angiotensin II stimulation of divalent cation influx (Mn 2ϩ quench of fura-2 fluorescence) was decreased significantly by AG1478. We conclude that epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca 2ϩ ] response to angiotensin II and that this process involves promotion of Ca 2ϩ influx.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca ²⁺ Influx in Afferent Arterioles

Che¹,

Carmines²

2002

Hypertension

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“…The main mechanism involved in the contraction of vascular smooth muscle by this agonist is considered to be produced through an increase in cytoplasmic Ca 2+ and phosphorylation of the regulatory light chains of myosin (Karaki et al, 1997). It is well known that vasoconstrictive agonists activate multiple pathways that modulate the contractile response of smooth muscle, and protein kinase C (PKC) (Horowitz et al, 1996), Rho family G proteins (Somlyo and Somlyo, 2000), nonreceptor tyrosine kinases (Hughes and Wijetunge, 1998) and extracellular signal-regulated kinases (ERK1/2) (Ishihata et al, 2002) have been shown to play roles in smooth muscle contraction. Since the leaf aqueous extract of T. procumbens affected contractile responses produced by NE, KCl and serotonine, it is suggested a possible involvement of non-specific but ultimate interference with the availability of Ca 2+ for the contractile process.…”

Section: Discussionmentioning

confidence: 99%

Vasorelaxant effects of aqueous leaf extract of <i>Tridax procumbens</i> on aortic smooth muscle isolated from the rat

Salahdeen

Murtala

2012

J. Smooth Muscle Res.

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Tridax procumbens is commonly used in traditional medicine in southern part of Nigeria for the treatment of hypertension. However, the mechanism of its antihypertensive properties remains unclear. Attempts were made to investigate the properties of direct actions of aqueous extract of the leaves of T. procumbens on mechanical responses of smooth muscles in aortic ring preparations isolated from the rat. Endothelium-intact aortic rings, isolated from the normotensive rats, had been pre-contracted with noradrenaline, and cumulative addition of the aqueous extract (0.15-1.05 mg/mL) to the bathing fluid induced a concentration-dependent relaxation. Aqueous extract of T. procumbens also attenuated the contractile responses to KCl and shifted the concentration-response curve to the right. The contractile responses to serotonin were also attenuated and the concentration-response curve was shifted to the right in the presence of the extract. The results of this study indicated that aqueous leaf extract of T. procumbens possesses vasodilatory effects on the aortic smooth muscles isolated from the rat. Based on these results, a possible mechanism involved in the relaxing actions of the extract on vascular smooth muscle was discussed. The results of this study may provide a scientific basis for the use of this extract to the treatment of hypertension in Nigerian traditional medicine.

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“…However, there is considerable evidence indicating that vasoconstrictors activate multiple ancillary pathways that modulate the contractile response (see reviews 2,3 ). Among the many pathways activated, protein kinase C, 2 Rho family G proteins, 3,4 nonreceptor tyrosine kinases, 5 and extracellular signal-regulated kinases (ERK1/2) 2,6 have been shown to play a role in smooth muscle contraction. Recently, stressactivated protein kinases have also been implicated in sustained contraction through regulation of the phosphorylation of heat shock protein (HSP) 27.…”

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confidence: 99%

Activation of p38 Mitogen-Activated Protein Kinases by Endothelin and Noradrenaline in Small Arteries, Regulation by Calcium Influx and Tyrosine Kinases, and Their Role in Contraction

Ohanian

Cunliffe

Ceppi

et al. 2001

ATVB

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Abstract-Small-artery responses to vasoconstrictor agonists are important for vascular function. To investigate the signaling pathways involved in contraction, we studied the activation and regulation of p38 mitogen-activated protein kinases (p38MAPKs) and heat shock protein (HSP) kinase by endothelin and noradrenaline in rat mesenteric arteries. Both vasoconstrictors activated p38␣ and/or p38␤ but not p38␥ or p38␦, leading to increased HSP kinase activity. p38MAPK activation by noradrenaline was maximum between 2 and 10 minutes and was wholly dependent on calcium influx but insensitive to the tyrosine kinase inhibitor herbimycin A. In contrast, endothelin induced a biphasic response, with activation at 2 and 10 minutes. The early activity was wholly dependent on calcium influx and inhibited by herbimycin A. The later activity was only 50% calcium dependent, was insensitive to herbimycin A, but was 50% inhibited by genistein, a nonselective tyrosine kinase inhibitor. With both agonists, p38MAPK activity returned to basal by 30 minutes. SB203580, a p38MAPK inhibitor, blocked agonist-induced HSP kinase activity, and herbimycin A inhibited activation by endothelin but not by noradrenaline. In addition, SB203580 inhibited noradrenaline-induced contraction but had little effect on contraction to endothelin. These data show that vasoconstrictors use different upstream activators of p38MAPK in vascular tissue and that the p38MAPK pathway is selectively implicated in the contractile response to noradrenaline in small arteries. Key Words: vasoconstrictors Ⅲ vascular smooth muscle Ⅲ heat shock proteins Ⅲ signal transduction V ascular tone is an important determinant of peripheral resistance and blood pressure, and abnormalities in small-artery contractility contribute to pathological states such as vasospasm and hypertension. 1 The major mechanism of smooth muscle contraction is an increase in cytoplasmic calcium and phosphorylation of the regulatory light chains of myosin. However, there is considerable evidence indicating that vasoconstrictors activate multiple ancillary pathways that modulate the contractile response (see reviews 2,3 ). Among the many pathways activated, protein kinase C, 2 Rho family G proteins, 3,4 nonreceptor tyrosine kinases, 5 and extracellular signal-regulated kinases (ERK1/2) 2,6 have been shown to play a role in smooth muscle contraction. Recently, stressactivated protein kinases have also been implicated in sustained contraction through regulation of the phosphorylation of heat shock protein (HSP) 27. 7 HSP27 belongs to a family of small HSPs that includes HSP20, myotonic dystrophy kinase-binding proteins, and crystallins. 8 Increased phosphorylation of HSP27 has been reported in response to a variety of vasoconstrictors in smooth muscle, 9 -12 and inhibition of HSP27 phosphorylation or interference with its function reduces contraction. 9 HSPs may also play a role in vascular diseases such as hypertension. For instance, stress-induced hypertension in rats increased the expression and phos...

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Role of tyrosine phosphorylation in excitation–contraction coupling in vascular smooth muscle

Cited by 43 publications

References 132 publications

Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca ²⁺ Influx in Afferent Arterioles

Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca ²⁺ Influx in Afferent Arterioles

Vasorelaxant effects of aqueous leaf extract of <i>Tridax procumbens</i> on aortic smooth muscle isolated from the rat

Activation of p38 Mitogen-Activated Protein Kinases by Endothelin and Noradrenaline in Small Arteries, Regulation by Calcium Influx and Tyrosine Kinases, and Their Role in Contraction

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Role of tyrosine phosphorylation in excitation–contraction coupling in vascular smooth muscle

Cited by 43 publications

References 132 publications

Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca 2+ Influx in Afferent Arterioles

Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca 2+ Influx in Afferent Arterioles

Vasorelaxant effects of aqueous leaf extract of <i>Tridax procumbens</i> on aortic smooth muscle isolated from the rat

Activation of p38 Mitogen-Activated Protein Kinases by Endothelin and Noradrenaline in Small Arteries, Regulation by Calcium Influx and Tyrosine Kinases, and Their Role in Contraction

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Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca ²⁺ Influx in Afferent Arterioles

Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca ²⁺ Influx in Afferent Arterioles