|alpha(1D)-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes|
|Fan, Lin-lin1; Ren, Shuang1; Zhou, Hong3; Wang, Ying2; Xu, Ping-xiang1; He, Jun-qi2; Luo, Da-li1|
|关键词||alpha(1D)-adrenergic receptor vascular smooth muscle cells receptor sensitivity receptor distribution Ca2+ signaling|
|刊名||ACTA PHARMACOLOGICA SINICA|
|WOS标题词||Science & Technology|
|类目[WOS]||Chemistry, Multidisciplinary ; Pharmacology & Pharmacy|
|研究领域[WOS]||Chemistry ; Pharmacology & Pharmacy|
|关键词[WOS]||SMOOTH-MUSCLE-CELLS ; ALPHA(1)-ADRENERGIC RECEPTORS ; BLOOD-PRESSURE ; CELLULAR-LOCALIZATION ; SIGNAL-TRANSDUCTION ; CA2+ ENTRY ; SUBTYPES ; HYPERTROPHY ; AORTA ; VASOCONSTRICTION|
Aim: It is unclear why alpha(1D)-adrenergic receptors (alpha(1D)-ARs) play a critical role in the mediation of peripheral vascular resistance and blood pressure in situ but function inefficiently when studied in vitro. The present study examined the causes for these inconsistencies in native alpha(1)-adrenergic functional performance between the vascular smooth muscle and myocytes.
Methods: The alpha(1)-adrenergic mediated contraction, Ca2+ signaling and the subcellular receptor distribution were evaluated using the Fluo-4, BODIPY-FL prazosin and subtype-specific antibodies.
Results: Rat aortic rings and freshly dissociated myocytes displayed contractile and increased intracellular Ca2+ responses to stimulation with phenylephrine (PE, 10 mu mol), respectively. However, the PE-induced responses disappeared completely in cultured aortic myocytes, whereas PE-enhanced Ca2+ transients were seen in cultured rat cardiac myocytes. Further studies indicated that alpha(1D)-ARs, the major receptor subtype responsible for the alpha(1)-adrenergic regulation of aortic contraction, were distributed both intracellularly and at the cell membrane in freshly dispersed aortic myocytes, similar to the alpha(1A)-AR subcellular localization in the cultured cardiomyocytes. In the cultured aortic myocytes, however, in addition to a marked decrease in their protein expression relative to the aorta, most labeling signals for alpha(1D)-ARs were found in the cytoplasm. Importantly, treating the culture medium with charcoal/dextran caused the reappearance of alpha(1D)-ARs at the cell surface and a partial restoration of the Ca2+ signal response to PE in approximately 30% of the cultured cells.
Conclusion: Reduction in alpha(1D)-AR total protein expression and disappearance from the cell surface contribute to the insensitivity of cultured vascular smooth muscle cells to alpha(1)-adrenergic receptor activation.
|项目编号||30772574 ; 7082018|
|资助机构||National Natural Science Foundation ; Beijing Municipal ; Scientific Research Common Program of the Beijing Municipal Commission of Education ; Beijing Natural Science Foundation|
|作者单位||1.Capital Med Univ, Dept Pharmacol, Beijing 100069, Peoples R China|
2.Capital Med Univ, Dept Biochem, Beijing 100069, Peoples R China
3.Peking Univ, Med Sci Ctr, Dept Pharmacol, Beijing 100191, Peoples R China
|Fan, Lin-lin,Ren, Shuang,Zhou, Hong,et al. alpha(1D)-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes[J]. ACTA PHARMACOLOGICA SINICA,2009,30(12):1585-1593.|
|APA||Fan, Lin-lin.,Ren, Shuang.,Zhou, Hong.,Wang, Ying.,Xu, Ping-xiang.,...&Luo, Da-li.(2009).alpha(1D)-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes.ACTA PHARMACOLOGICA SINICA,30(12),1585-1593.|
|MLA||Fan, Lin-lin,et al."alpha(1D)-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes".ACTA PHARMACOLOGICA SINICA 30.12(2009):1585-1593.|