Structure and Function of the Adrenergic Receptor Family

Roth, Neil S.; Lefkowitz, Robert J.; Caron, Marc G.

doi:10.1007/978-1-4684-6015-5_20

Cited by 11 publications

(8 citation statements)

References 57 publications

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“…/I-Adrenergic receptors can become desensitized via phosphorylation by protein kinase A or the /3-adrenergic receptor kinase @ARK) [l-3]. Phosphorylation of the receptors by PARK, followed by binding of the inhibitor protein B-arrestin to the phosphorylated receptors represents the most rapid and quantitatively most important mechanism causing agonist-induced, homologous desensitization of p-adrenergic receptors [7]. In addition to phosphorylating Pz-adrenergic receptors, PARK can also phosphorylate ol,-adrenergic and muscarinic receptors as well as the 'light receptor' rhodopsin [g-lo].…”

Section: Signal Transductionmentioning

confidence: 99%

Purification and functional characterization of β‐adrenergic receptor kinase expressed in insect cells

et al. 1993

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The B-adrenerglc receptor kinase mediates agomst-dependent phosphorylatlon of /&adrenerglc receptors, which 1s thought to represent the first step of homologous desensitization.We have expressed bovine and human BARK1 in St9 cells and purified them to apparent homogeneity m milligram quantities. The &-values of the enzyme were 3.8 PM for rhodopsin and 22 PM for ATP: the r',,,,, -value was 9.9 mol phosphate/m01 BARK/mm.These data indicate that the two recombinant kmases were at least as active as preparations previously obtained from bovme brain There were no differences in the functional activity of human and bovine BARK.

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Section: Signal Transductionmentioning

confidence: 99%

Purification and functional characterization of β‐adrenergic receptor kinase expressed in insect cells

et al. 1993

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“…Norepinephrine and epinephrine are catecholamines (CA) released from synaptic nerves and the adrenal gland that mediate systemic responses to nutritional stressors (Cannon and De la Paz 1911). CA mobilize plasma glucose by suppressing insulin secretion from the pancreatic β-cell (Katada and Ui 1981, Laychock and Bilgin 1987) Nine isoforms of adrenergic receptors (ADR) mediate the actions of CA (Roth et al 1991). Predominantly the β isoforms (ADRβ1, ADRβ2, ADRβ3) couple to stimulatory G proteins (G s ).…”

Section: Introductionmentioning

confidence: 99%

Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat islets and Min6 cells

Kelly

Camacho

Pendarvis

et al. 2018

Molecular and Cellular Endocrinology

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Insulin secretion is stimulated by glucose metabolism and inhibited by catecholamines through adrenergic receptor stimulation. We determined whether catecholamines suppress oxidative metabolism in β-cells through adrenergic receptors. In Min6 cells and isolated rat islets, epinephrine decreased oxygen consumption rates compared to vehicle control or co-administration of epinephrine with α2-adrenergic receptor antagonist yohimbine. Epinephrine also decreased forskolin-stimulated oxygen consumption rates, indicating cAMP dependent and independent actions. Furthermore, glucose oxidation rates were decreased with epinephrine, independent of the exocytosis of insulin, which was blocked with yohimbine. We evaluated metabolic targets through proteomic analysis after 4 h epinephrine exposure that revealed 466 differentially expressed proteins that were significantly enriched for processes including oxidative metabolism, protein turnover, exocytosis, and cell proliferation. These results demonstrate that acute α2-adrenergic stimulation suppresses glucose oxidation in β-cells independent of nutrient availability and insulin exocytosis, while cAMP concentrations are elevated. Proteomics and immunoblots revealed changes in electron transport chain proteins that were correlated with lower metabolic reducing equivalents, intracellular ATP concentrations, and altered mitochondrial membrane potential implicating a new role for adrenergic control of mitochondrial function and ultimately insulin secretion.

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“…Manipulation of the cDNA encoding a receptor followed by expression of the mutant protein in a cell model allows detailed analysis of the role of specific receptor domains and individual residues. This approach has been widely utilized and has resulted in important advancement in our understanding of G protein-coupled receptor signaling (1). However, it has become increasingly apparent that the choice of cell model used for gene transfer experiments significantly impacts the receptor properties that are observed (2).…”

mentioning

confidence: 99%

“…In both species, CCK A receptors bind the endogenous hormone cholecystokinin (CCK) 1 with high affinity. A similar pattern of cell signals and biological responses is in turn triggered in both rats and mice.…”

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confidence: 99%

Species Differences between Rat and Mouse CCKAReceptors Determine the Divergent Acinar Cell Response to the Cholecystokinin Analog JMV-180

Ji¹,

Kopin²,

Logsdon³

2000

Journal of Biological Chemistry

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The cholecystokinin (CCK) analog JMV-180 acts as a partial agonist in rats and a full agonist in mice. Whether this functional variability is due to species differences in CCK receptor structure or to alterations in the cellular environment is unknown. To address this question, an adenoviral construct encoding the rat CCK A receptor (AdCCK A R) was used to express the rat receptor in acini from CCK A receptor-deficient mice (CCK A R ؊/؊). Infection of CCK A R ؊/؊ acini in vitro with pAdCCK A R led to a time-dependent increase in 125 I-CCK 8 binding. The affinity for JMV-180 of the adenovirally transferred rat and the endogenous mouse CCK A receptors was not different. In native mouse acini, JMV-180 acted as a full agonist (both stimulation and inhibition of amylase release). In contrast, in mouse acini expressing pAdCCK A R JMV-180 acted as a partial agonist (only stimulation of amylase release). In addition, the pattern of protein synthesis induced by JMV-180 in CCK A R ؊/؊ mouse acini infected with AdCCK A R resembled the pattern observed in wild-type rats (lack of inhibition) rather than the respective pattern in wild-type mice (inhibition). These data suggest that species differences in the CCK A receptor of rats and mice account for the observed divergence in the acinar cell response to JMV-180.Gene transfer studies provide a powerful approach to investigate the correlation between receptor structure and function. Manipulation of the cDNA encoding a receptor followed by expression of the mutant protein in a cell model allows detailed analysis of the role of specific receptor domains and individual residues. This approach has been widely utilized and has resulted in important advancement in our understanding of G protein-coupled receptor signaling (1). However, it has become increasingly apparent that the choice of cell model used for gene transfer experiments significantly impacts the receptor properties that are observed (2). Differentiated cells express specific subsets of proteins that interact with G protein-linked receptors; examples include G proteins, arrestins, G protein receptor kinases, and RGS proteins (3). The cell model may therefore exert a major influence on the outcome of receptor structure-function studies.Recently it was suggested that interspecies variation in cellular milieu might explain observed differences between the drug-induced responses of the rat versus the mouse CCK A receptor (4). In both species, CCK A receptors bind the endogenous hormone cholecystokinin (CCK) 1 with high affinity. A similar pattern of cell signals and biological responses is in turn triggered in both rats and mice. In contrast, the CCK analog JMV-180 acts as a partial agonist in the rat and a full agonist in the mouse (5-7). Differences between partial and full CCK agonists are striking in the pancreatic acinar cell. Full agonists (e.g. CCK-8) show marked differences in biological effects at both physiologic and supra-physiologic concentrations. At physiologic concentrations, full agonists cause increases in...

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Structure and Function of the Adrenergic Receptor Family

Cited by 11 publications

References 57 publications

Purification and functional characterization of β‐adrenergic receptor kinase expressed in insect cells

Purification and functional characterization of β‐adrenergic receptor kinase expressed in insect cells

Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat islets and Min6 cells

Species Differences between Rat and Mouse CCKAReceptors Determine the Divergent Acinar Cell Response to the Cholecystokinin Analog JMV-180

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