23 Result(s)
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Article
Open AccessEstablishment of multi-stage intravenous self-administration paradigms in mice
Genetically tractable animal models provide needed strategies to resolve the biological basis of drug addiction. Intravenous self-administration (IVSA) is the gold standard for modeling psychostimulant and opi...
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Open AccessA cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion
Field cancerization is a premalignant process marked by clones of oncogenic mutations spreading through the epithelium. The timescales of intestinal field cancerization can be variable and the mechanisms drivi...
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Open AccessAdipocyte β-arrestin-2 is essential for maintaining whole body glucose and energy homeostasis
β-Arrestins are major regulators of G protein-coupled receptor-mediated signaling processes. Their potential roles in regulating adipocyte function in vivo remain unexplored. Here we report the novel finding t...
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Open Accessβ-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions
β-arrestins are critical signalling molecules that regulate many fundamental physiological functions including the maintenance of euglycemia and peripheral insulin sensitivity. Here we show that inactivation o...
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Article
Antidepressants at work
Structures of the serotonin transporter protein SERT in complex with two different antidepressants shed light on how these drugs act, and point to possible targets for future drug development. See Article ...
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Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs
The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumours; howeve...
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Article
Methylphenidate amplifies the potency and reinforcing effects of amphetamines by increasing dopamine transporter expression
Methylphenidate (MPH) is commonly diverted for recreational use, but the neurobiological consequences of exposure to MPH at high, abused doses are not well defined. Here we show that MPH self-administration in...
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Open AccessThe role of GRK6 in animal models of Parkinson's Disease and L-DOPA treatment
G protein-coupled Receptor Kinase 6 (GRK6) belongs to a family of kinases that phosphorylate GPCRs. GRK6 levels were found to be altered in Parkinson's Disease (PD) and D2 dopamine receptors are supersensitive in...
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μ-Opioid receptor desensitization by β-arrestin-2 determines morphine tolerance but not dependence
Morphine is a powerful pain reliever, but also a potent inducer of tolerance and dependence. The development of opiate tolerance occurs on continued use of the drug such that the amount of drug required to eli...
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Article
Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter
Disruption of the mouse dopamine transporter gene results in spontaneous hyperlocomotion despite major adaptive changes, such as decreases in neurotransmitter and receptor levels. In homozygote mice, dopamine ...
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Article
The chimaeras speak again
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Article
Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases
RHODOPSIN kinase1 and β-adrenergic receptor kinase (β ARK)2 are related members of a serine/threonine kinase family that specifically initiate deactivation of G-protein-coupled receptors. After stimulus-mediated ...
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Article
Cloning and expression of a functional serotonin transporter from rat brain
SELECTIVE antagonism of serotonin (5-hydroxytryptamine, 5HT) and noradrenaline transport by antidepressants is a key element in the 'amine' hypothesis of affective disorders1. Uptake2,3 and/or transport sites4,5 ...
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Article
Molecular cloning and expression of the gene for a human D1 dopamine receptor
THE diverse physiological actions of dopamine are mediated by its interaction with two basic types of G protein-coupled receptor, D1 and D2, which stimulate and inhibit, respectively, the enzyme adenylyl cyclase1
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The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor
The recent cloning of the complementary DNAs and/or genes for several receptors linked to guanine nucleotide regulatory proteins including the adrenergic receptors (α1, α2A, α2B, β1, β2)1–7 several subtypes of t...
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Removal of phosphorylation sites from the β2-adrenergic receptor delays onset of agonist-promoted desensitization
Eukaryotic cells have evolved a variety of mechanisms for dampening their responsiveness to hormonal stimulation in the face of sustained activation. The mechanisms for such processes, collectively referred to...
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An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins
Plasma membrane receptors for hormones, drugs, neurotransmit-ters and sensory stimuli are coupled to guanine nucleotide regulatory proteins. Recent cloning of the genes and/or cDNAs for several of these recep...
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Cross-talk between cellular signalling pathways suggested by phorbol-ester-induced adenylate cyclase phosphorylation
Receptor-mediated activation of both adenylate cyclase and phosphatidylinositide hydrolysis systems occurs through guanine nucleotide regulatory proteins and ultimately leads to specific activation of either c...
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Light-dependent phosphorylation of rhodopsin by β-adrenergic receptor kinase
The structural components involved in transduction of extracellular signals as diverse as a photon of light im**ing on the retina or a hormone molecule im**ing on a cell have been highly conserved. These c...
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Article
Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin
The adenylate cyclase system, which consists of a catalytic moiety and regulatory guanine nucleotide-binding proteins, provides the effector mechanism for the intracellular actions of many hormones and drugs1. Th...
