Regulation of alpha-1B adrenergic receptor localization, trafficking, function, and stability

Toews, Myron L.; Prinster, Steven C.; Schulte, Nancy A.

doi:10.1016/j.lfs.2003.09.024

Cited by 25 publications

(18 citation statements)

References 42 publications

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“…However, the three different subtypes have been found to have different coupling efficiencies or distinct patterns of activation for different responses (Theroux et al, 1996; Zhong and Minneman, 1999;Toews et al, 2003). In general, the recombinant ␣ 1A -AR expressed in cultured cells seemed to be more efficient than the ␣ 1B -and ␣ 1D -ARs in activating IP formation and causing a release of intracellular calcium.…”

Section: Discussionmentioning

confidence: 99%

“…So far, three distinct ␣ 1 -AR subtypes have been found, designated as ␣ 1A -, ␣ 1B -, and ␣ 1D -ARs (Cotecchia et al, 1988;Schwinn et al, 1990;Lomasney et al, 1991). Each subtype shows distinct pharmacological characteristics and couples mainly via G q/11 to the activation of phospholipase C and mitogen-activated protein kinase (MAPK) with different efficiencies (Zhong and Minneman, 1999;Koshimizu et al, 2002;Toews et al, 2003).…”

mentioning

confidence: 99%

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Pharmacological Characterization and Cross Talk of α_1A- and α_1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

Israilova

Tanaka²,

Suzuki³

et al. 2004

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacological Characterization and Cross Talk of α_1A- and α_1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

Israilova

Tanaka²,

Suzuki³

et al. 2004

J Pharmacol Exp Ther

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“…Therefore, we hypothesized that the lack of increase in NE-stimulated [ 3 H]InsP formation in cells co-expressing ␣ 1B -and ␣ 1D -ARs might potentially be due to agonist-induced internalization of ␣ 1D -ARs. Previous reports have shown that ␣ 1B -ARs are rapidly internalized upon agonist stimulation (47). However, there are no previous reports investigating ␣ 1D -AR internalization, because this receptor is almost exclusively intracellular after heterologous expression.…”

Section: Role Of ␣ 1b -/␣ 1d -Ar Heterodimerization In ␣ 1d -Ar Couplmentioning

confidence: 96%

Cell Surface Expression of α1D-Adrenergic Receptors Is Controlled by Heterodimerization with α1B-Adrenergic Receptors

Hague

Uberti

Chen

et al. 2004

Journal of Biological Chemistry

151

140

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␣ 1 -Adrenergic receptors (ARs) belong to the large Class I G protein-coupled receptor superfamily and comprise three subtypes (␣ 1A , ␣ 1B , and ␣ 1D ). Previous work with heterologously expressed C-terminal green fluorescent protein (GFP)-tagged ␣ 1 -ARs showed that ␣ 1A -and ␣ 1B -ARs localize to the plasma membrane, whereas ␣ 1D -ARs accumulate intracellularly. We recently showed that ␣ 1D -and ␣ 1B -ARs form heterodimers, whereas ␣ 1D -and ␣ 1A -ARs do not. Here, we examined the role of heterodimerization in regulating ␣ 1D -AR localization using both confocal imaging of GFP-or CFPtagged ␣ 1 -ARs and a luminometer-based surface expression assay in HEK293 cells. Co-expression with ␣ 1B -ARs caused ␣ 1D -ARs to quantitatively translocate to the cell surface, but co-expression with ␣ 1A -ARs did not. Truncation of the ␣ 1B -AR extracellular N terminus or intracellular C terminus had no effect on surface expression of ␣ 1D -ARs, suggesting primary involvement of the hydrophobic core. Co-transfection with an uncoupled mutant ␣ 1B -AR (⌬12␣ 1B ) increased both ␣ 1D -AR surface expression and coupling to norepinephrine-stimulated Ca 2؉ mobilization. Finally, GFP-tagged ␣ 1D -ARs were not detected on the cell surface when expressed in rat aortic smooth muscle cells that express no endogenous ARs, but were almost exclusively localized on the surface when expressed in DDT 1 MF-2 cells, which express endogenous ␣ 1B -ARs. These studies demonstrate that ␣ 1B /␣ 1D -AR heterodimerization controls surface expression and functional coupling of ␣ 1D -ARs, the N-and Cterminal domains are not involved in this interaction, and that ␣ 1B -AR G protein coupling is not required. These observations may be relevant to many other Class I G protein-coupled receptors, where the functional consequences of heterodimerization are still poorly understood.

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“…Reperfusion for 2 min after 20 min ischemia, however, caused a selective loss of ␣ 1 -AR from the caveolar fraction. Loss of ␣ 1 -AR from caveolae, rather than providing an explanation for the heightened response in reperfusion, most likely reflects receptor desensitization (45).…”

Section: Reperfusion Of Ischemic Rat Hearts Increases Pip 2 Independementioning

confidence: 99%

Inositol phospholipids localized to caveolae in rat heart are regulated by α₁-adrenergic receptors and by ischemia-reperfusion

Lanzafame¹,

Turnbull²,

Amiramahdi³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Inositol phospholipids localized to caveolae in rat heart are regulated by ␣1-adrenergic receptors and by ischemia-reperfusion. Am J Physiol Heart Circ Physiol 290: H2059 -H2065, 2006. First published December 22, 2005; doi:10.1152/ajpheart.01210.2005.-Postischemic reperfusion of rat or mouse hearts causes generation of inositol (1,4,5)trisphosphate [Ins(1,4,5)P3] and the initiation of arrhythmias. In the current study we investigated the possibility that the enhanced Ins(1,4,5)P3 generation in postischemic reperfusion was associated with an increased availability of the precursor lipid phosphatidylinositol(4,5)bisphosphate (PIP2) for ␣1-adrenergic receptor-activated phospholipase C (PLC). Isolated-perfused rat hearts were labeled with [3 H]inositol and subjected to ischemia-reperfusion or stimulation with norepinephrine under normoxic conditions. Caveolar fractions were prepared by buoyant density sucrose gradient centrifugation. [3 H]PIP2 was concentrated in caveolae, along with G␣q and PLC␤1b. Caveolae contained only 27.3 Ϯ 6.9% (means Ϯ SE, n ϭ 6) of the total ␣ 1-adrenergic receptor complement of the heart. These did not migrate to PIP2-containing caveolar fractions with norepinephrine stimulation under normoxic conditions, even though caveolar PIP2 was depleted. In contrast, [3 H]PIP2 in caveolae increased during 2 min of reperfusion, independently of norepinephrine release and thus of ␣1-adrenergic receptor activation. The increased PIP2 in the caveolar fractions where signaling proteins are concentrated may be critical for the heightened generation of Ins(1,4,5)P 3 in early reperfusion. lipid signaling; light lipid rafts; phospholipase C; Gq; caveolin BRIEF PERIODS OF ISCHEMIA-REPERFUSION in the rat and mouse heart cause norepinephrine release, activation of ␣ 1 -adrenergic receptors (␣ 1 -AR), and substantial generation of inositol (1,4,5)trisphosphate [Ins(1,4,5)P 3 ] associated with the onset of arrhythmogenesis (1, 2, 13, 24, 41). Ins(1,4,5)P 3 is generated from sarcolemmal phosphatidylinositol(4,5)bisphosphate (PIP 2 ) following activation of phospholipase C (PLC). We addressed the possibility that increased availability of PIP 2 or factors required for PLC activation contributed to the heightened generation of Ins(1,4,5)P 3 during postischemic reperfusion.PIP 2 is generated from phosphatidylinositol most commonly by phosphorylation to PI(4)P, followed by further phosphorylation to PI(4,5)P 2 (9) and to a lesser extent by sequential 5Ј and 4Ј phosphorylation (23). PIP 2 is critically involved in myocardial responses. In addition to Ins(1,4,5)P 3 , PLC cleavage of PIP 2 generates sn-1,2-diacylglycerol, an activator of PKC isoforms (31). PIP 2 is also the precursor of PIP 3 , an important factor in cardiomyocyte development and cytoprotection (43). Further to these roles as precursor to other active molecules, PIP 2 itself acts as a second messenger by activating phospholipase D activity in the heart (25). PIP 2 is critically important in stabilizing various ion channels and transporters (22, 32) an...

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Regulation of alpha-1B adrenergic receptor localization, trafficking, function, and stability

Cited by 25 publications

References 42 publications

Pharmacological Characterization and Cross Talk of α_1A- and α_1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

Pharmacological Characterization and Cross Talk of α_1A- and α_1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

Cell Surface Expression of α1D-Adrenergic Receptors Is Controlled by Heterodimerization with α1B-Adrenergic Receptors

Inositol phospholipids localized to caveolae in rat heart are regulated by α₁-adrenergic receptors and by ischemia-reperfusion

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Regulation of alpha-1B adrenergic receptor localization, trafficking, function, and stability

Cited by 25 publications

References 42 publications

Pharmacological Characterization and Cross Talk of α1A- and α1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

Pharmacological Characterization and Cross Talk of α1A- and α1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

Cell Surface Expression of α1D-Adrenergic Receptors Is Controlled by Heterodimerization with α1B-Adrenergic Receptors

Inositol phospholipids localized to caveolae in rat heart are regulated by α1-adrenergic receptors and by ischemia-reperfusion

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Product

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Pharmacological Characterization and Cross Talk of α_1A- and α_1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

Pharmacological Characterization and Cross Talk of α_1A- and α_1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

Inositol phospholipids localized to caveolae in rat heart are regulated by α₁-adrenergic receptors and by ischemia-reperfusion