Phospholipase D1 is involved in α‐adrenergic contraction of murine vascular smooth muscle

Phospholipase D1 is involved in α‐adrenergic contraction of murine vascular smooth muscle
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磷脂酶 D1 参与小鼠血管平滑肌的α肾上腺素能收缩

DOI:
10.1096/fj.13-237925
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发表时间:
2014
期刊:
The FASEB Journal
影响因子:
--
通讯作者:
Hofmann F
Hofmann F
中科院分区:
--
文献类型:
--
作者:
Wegener JW;Loga F;Stegner D;Nieswandt B;Hofmann F

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α1-肾上腺素能刺激增加哺乳动物的血管张力。这一过程涉及许多细胞内信号传导途径,包括通过磷脂酶C、甘油二酯(DAG)和蛋白激酶C进行信号传导。到目前为止,尚不确定是否通过磷脂酶D(PLD)和PLD衍生的DAG参与这一过程。我们询问PLD是否参与血管平滑肌中α1-肾上腺素能介导的信号传导。通过离体主动脉环的肌电图和使用小鼠后肢灌注模型的压力记录评估α1肾上腺素能诱导的收缩。比较研究了PLD抑制剂1-丁醇(IC500.15 vol%)和无活性同系物2-丁醇的作用。1-丁醇对PLD的抑制可特异性降低α1-肾上腺素能诱导的收缩和α1-肾上腺素能诱导的压力增加,分别为最大值的10%和40%。1-丁醇不影响高细胞外钾、血栓烷类似物U46619或佛波酯诱导的主动脉收缩。在缺乏PLD 1的小鼠(Pld 1-/-小鼠)或选择性缺乏平滑肌CaV 1.2通道的小鼠(sm-CaV 1.2-/-小鼠)中不存在1-丁醇的作用,但在杂合对照小鼠中仍然存在。血管平滑肌的α1-肾上腺素能收缩涉及PLD 1的激活,其控制α1-肾上腺素能诱导的CaV1.2通道活性的一部分。Wegener,J. W.,Loga,F.,Stegner,D.,尼斯旺特,B.,Hofmann,F.磷脂酶D1参与鼠血管平滑肌的α1-肾上腺素能收缩。FASEB J.28,1044-1048(2014)。www.fasebj.org
α1‐Adrenergic stimulation increases blood vessel tone in mammals. This process involves a number of intracellular signaling pathways that include signalingviaphospholipase C, diacylglycerol (DAG), and protein kinase C. So far, it is not certain whether signalingviaphospholipase D (PLD) and PLD‐derived DAG is involved in this process. We asked whether PLD participates in the α1‐adrenergic‐mediated signaling in vascular smooth muscle. α1‐Adrenergic‐induced contraction was assessed by myography of isolated aortic rings and by pressure recordings using the hindlimb perfusion model in mice. The effects of the PLD inhibitor 1‐butanol (IC500.15 vol%) and the inactive congener 2‐butanol were comparatively studied. Inhibition of PLD by 1‐butanol reduced specifically the α1‐adrenergic‐induced contraction and the α1‐adrenergic‐induced pressure increase by 10 and 40% of the maximum, respectively. 1‐Butanol did not influence the aortic contractions induced by high extracellular potassium, by the thromboxane analog U46619, or by a phorbol ester. The effects of 1‐butanol were absent in mice that lack PLD1 (Pld1–/–mice) or that selectively lack the CaV1.2 channel in smooth muscle (sm‐CaV1.2–/–mice) but still present in the heterozygous control mice. α1‐Adrenergic contraction of vascular smooth muscle involves activation of PLD1, which controls a portion of the α1‐adrenergic‐induced CaV1.2 channel activity.—Wegener, J. W., Loga, F., Stegner, D., Nieswandt, B., Hofmann, F. Phospholipase D1 is involved in α1‐adrenergic contraction of murine vascular smooth muscle.FASEB J.28, 1044–1048 (2014). www.fasebj.org
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