Mitogen-activated protein kinase activation: An alternate signaling pathway for sustained vascular smooth muscle contraction

Epstein, Aaron; Throckmorton, Douglas C.; Brophy, Colleen M.

doi:10.1016/s0741-5214(97)70196-4

Cited by 48 publications

(35 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports have also suggested that ERK is involved in regulating agonist-induced vasoconstriction. For example, inhibition of MAPK activation has been shown to attenuate not only 5-hydroxytryptamine 2A (Florian and Watts, 1998;Banes et al, 1999) but also angiotensin (Epstein et al, 1997)-and ␣ 1 -AR (DiSalvo et al, 1993) mediated vasoconstriction. Possible mechanisms by which ERK activation has been proposed to affect contractile responses include phosphorylation of caldesmon (Adam et al, 1989;Hedges et al, 2000) or myosin (Jin et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Relationship between α₁-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery

Hague

Gonzalez-Cabrera

Jeffries

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The endogenous adrenergic agonists norepinephrine (NE) and epinephrine regulate vascular tone by stimulating ␣ 1 -adrenergic receptors (ARs) on smooth muscle cells to cause contraction. In addition, ␣ 1 -ARs also couple to growth factor pathways, through stimulation of mitogen-activated protein kinases (MAPKs). MAPKs are a family of serine-threonine kinases that include extracellular signal-regulated kinase (ERK) and a variety of other kinases that are able to activate transcription factors when stimulated. We examined ␣ 1 -AR stimulation of contraction and ERK activation in the bovine inferior alveolar artery (BIAA), using in vitro contraction studies and Western blotting. Using antagonists selective for individual adrenergic receptor types, we found that only ␣ 1 -ARs were coupled to ERK activation and contraction. NE stimulated contraction (EC 50 ϭ 11 M) and ERK activation (EC 50 ϭ 21 M) with similar potency. Using ␣ 1 -AR subtype-selective antagonists, we identified the ␣ 1 -AR subtypes coupled to each response. Affinity values for ␣ 1 -AR subtype-selective antagonists were consistent with ␣ 1A -AR-mediated contraction. In contrast, simultaneous treatment with concentrations of these antagonists selective for each ␣ 1 -AR subtype (␣ 1A -, ␣ 1B -, and ␣ 1D -AR) was required to inhibit ERK activation, suggesting that all three ␣ 1 -ARs activate ERK in BIAA. Transmural electrical stimulation of BIAA segments resulted in activation of ERK, which was inhibited by the ␣ 1 -ARselective antagonist BE 2254 (2-[[␤-(4-hydroxyphenyl)ethyl]aminomethyl]-1-tetralone). These data suggest that in an intact artery, NE released from sympathetic nerves stimulates ␣ 1 -ARs to cause contraction and ERK activation, and that redundancy among subtypes exists for ␣ 1 -AR activation of ERK.The sympathetic nervous system controls peripheral vascular resistance by release of norepinephrine (NE) and epinephrine, which stimulate ␣ 1 -adrenergic receptors (ARs) on vascular smooth muscle cells. Molecular cloning and radioligand binding studies using selective antagonists have identified three distinct ␣ 1 -AR subtypes (␣ 1A -, ␣ 1B -, and ␣ 1D -AR).

show abstract

Section: Discussionmentioning

confidence: 99%

Relationship between α₁-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery

Hague

Gonzalez-Cabrera

Jeffries

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…For example, activation of the Erk MAPK pathway is important to vascular smooth muscle mitogenesis stimulated by 5-HT, 16 and 5-HT 2A receptor-mediated contraction is clearly tyrosine kinase/Erk MAPK dependent. [17][18][19]28,29 In contrast, the involvement of the tyrosine kinase or kinases/Erk MAPK pathway in ET-1-induced contraction is less clear. ET-1 acting at ET A receptors possesses the ability to activate the Erk MAPK pathway in human and rat vascular smooth muscle.…”

Section: Discussionmentioning

confidence: 99%

“…ET-1 acting at ET A receptors possesses the ability to activate the Erk MAPK pathway in human and rat vascular smooth muscle. 30,31 Only a few reports demonstrate that ET-1-induced contraction can be blocked by tyrosine kinase inhibitors, 29 and although the MEK inhibitor PD098059 was able to reduce ET-1-induced contraction in the isolated rat uterus, 32 no reports specifically implicate the Erk MAPK pathway in arterial contraction in response to ET-1. Interestingly, the ability of ET-1 to act as a direct mitogen is not universally found in that some investigators report that ET-1 could activate the MAPK pathway in smooth muscle but was a poor mitogen.…”

Section: Discussionmentioning

confidence: 99%

5-Hydroxytryptamine–Induced Potentiation of Endothelin-1– and Norepinephrine-Induced Contraction Is Mitogen-Activated Protein Kinase Pathway Dependent

Watts

2000

Hypertension

View full text Add to dashboard Cite

Abstract-5-Hydroxytryptamine (5-HT)-induced arterial contraction depends on activation of the tyrosine kinasedependent extracellular signal-regulated mitogen-activated protein kinase (Erk MAPK) pathway. The importance of 5-HT in the control of peripheral resistance has been questioned because circulating free levels of 5-HT are low (in the nanomolar range). We tested the hypothesis that physiologically relevant concentrations of 5-HT potentiate arterial contraction in response to agonists proved to have importance in blood pressure maintenance (norepinephrine [NE] and endothelin-1 [ET-1]) in a tyrosine kinase-and an Erk MAPK-dependent manner. Strips of endothelium-denuded rat tail artery were used for the measurement of isometric force. The general tyrosine kinase inhibitor genistein (5 mol/L) and the inhibitor of MAPK/Erk kinase activation PD098059 (10 mol/L) shifted concentration-response curves to 5-HT (1ϫ10 Ϫ9 to 3ϫ10 Ϫ4 mol/L) rightward but did not shift concentration-response curves to NE or ET-1. In separate experiments, 5-HT (10 nmol/L) potentiated contraction in response to NE (20 nmol/L) by Ϸ200% to 300% and to ET-1 (0.3 and 1 nmol/L) by 640% and 180%, respectively. Genistein and PD098059 significantly (66% to 100%) reduced 5-HT-induced potentiation of both NE (20 nmol/L)-and ET-1 (0.3 and 1 nmol/L)-induced contraction. Thus, these data support the ability of low physiological concentrations of 5-HT to amplify arterial responses to hormones with bona fide effects on blood pressure in the novel manner of depending on a tyrosine kinase/Erk MAPK pathway. Although these findings were generated in large arteries, we speculate that they may be applicable to vascular functioning in the deoxycorticosterone acetate salt model of hypertension in which all 3 hormones, 5-HT, NE, and ET-1, have been implicated as causal factors. Key Words: norepinephrine Ⅲ endothelin Ⅲ protein kinases Ⅲ arteries Ⅲ hormones S ince its discovery in serum in 1948, 1 5-hydroxytryptamine (5-HT [serotonin]) has been of interest to the cardiovascular researcher. 5-HT has been implicated in numerous cardiovascular diseases; vascular reactivity to 5-HT is increased in arteries from animals with different forms of hypertension 2 and atherosclerosis. 3 However, it has been argued that 5-HT plays an insignificant role in the physiological control of blood vessel tone because uptake of 5-HT by platelets, adrenergic nerves, or both causes circulating levels of 5-HT to be low (estimated to be 15 to 120 nmol/L 4 ) and out of a range that can directly cause constriction. One manner by which physiological concentrations of 5-HT may exert an effect on vascular tone is through the potentiation of vascular contraction in response to other vasoactive substances.5-HT-stimulated potentiation of agonist-induced contraction has classically been studied in the tail artery of the rat. [5][6][7] Norepinephrine (NE) was one of the first agonists established to be potentiated by 5-HT. The list of hormones of which contraction can be potentiated by 5-HT has grow...

show abstract

“…On the other hand, JNK / SAPK and p38 MAPK are implicated in responses to cellular stress, inflammation, and apoptosis. p42 / p44 MAPK may play a role in vascular smooth muscle contraction (11). Moreover, p42 / p44 MAPK may be an important regulator for rabbit basilar artery contraction (12).…”

Section: +mentioning

confidence: 99%

p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats

Kwon

Fang

et al. 2004

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. We investigated whether p42 / p44 mitogen-activated protein kinase (MAPK) and / or p38 MAPK participates in the regulation of vascular smooth muscle contraction by endothelin-1 (ET-1) in Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). ET-1 (10 nM) induced a sustained contraction in WKY and SHR aortas. PD98059 (100 m M), an inhibitor of p42/ p44 MAPK kinase, partially attenuated the ET-1-induced contraction in WKY and SHR. However, SB203580 (10 m M), an inhibitor of p38 MAPK, relaxed the ET-1-induced contraction to the resting levels in SHR, but not in WKY. ET-1 (10 nM) increased phosphorylation of both p42 / p44 MAPK and p38 MAPK in WKY and SHR. However, in SHR, p38 MAPK phosphorylation in response to ET-1 stimulation was increased more than in WKY. PD98059 (100 m M) and SB203580 (10 m M) abolished the phosphorylation of p42 / p44 MAPK and p38 MAPK in response to ET-1 stimulation in WKY and SHR, respectively. On the other hand, SB203580 (10 mM) did not affect myosin light chain (MLC) phosphorylation in response to ET-1 (10 nM) stimulation in WKY and SHR. From these results, it is concluded that p42 / p44 MAPK and/ or p38 MAPK partially regulates the ET-1-induced vasoconstriction in WKY. However, p38 MAPK, rather than p42 / p44 MAPK, activation plays an important role for the maintenance of ET-1-induced vasoconstriction in SHR through a MLC phosphorylationindependent pathway.

show abstract

Mitogen-activated protein kinase activation: An alternate signaling pathway for sustained vascular smooth muscle contraction

Abstract: These data suggest that the activation of MAP kinase is associated with sustained vascular smooth muscle contractions. Pharmacologic manipulation of MAP kinase activation may lead to new approaches to treat pathologic circumstances of increased vasomotor tone such as vasospasm.

Cited by 48 publications

References 20 publications

Relationship between α₁-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery

Relationship between α₁-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery

5-Hydroxytryptamine–Induced Potentiation of Endothelin-1– and Norepinephrine-Induced Contraction Is Mitogen-Activated Protein Kinase Pathway Dependent

p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats

Contact Info

Product

Resources

About

Mitogen-activated protein kinase activation: An alternate signaling pathway for sustained vascular smooth muscle contraction

Abstract: These data suggest that the activation of MAP kinase is associated with sustained vascular smooth muscle contractions. Pharmacologic manipulation of MAP kinase activation may lead to new approaches to treat pathologic circumstances of increased vasomotor tone such as vasospasm.

Cited by 48 publications

References 20 publications

Relationship between α1-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery

Relationship between α1-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery

5-Hydroxytryptamine–Induced Potentiation of Endothelin-1– and Norepinephrine-Induced Contraction Is Mitogen-Activated Protein Kinase Pathway Dependent

p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats

Contact Info

Product

Resources

About

Relationship between α₁-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery

Relationship between α₁-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery