Downregulation of caveolin by chronic β-adrenergic receptor stimulation in mice

1997 ◽  
Vol 273 (6) ◽  
pp. C1957-C1962 ◽  
Author(s):  
Naoki Oka ◽  
Kuniya Asai ◽  
Raymond K. Kudej ◽  
John G. Edwards ◽  
Yoshiyuki Toya ◽  
...  
Keyword(s):  
G Proteins ◽  
Adrenergic Receptor ◽  
Skeletal Muscles ◽  
Ventricular Myocardium ◽  
Northern Blotting ◽  
Receptor Stimulation ◽  
Caveolin 1 ◽  
Gradient Fractionation ◽  
The Brain ◽  
Isoproterenol Infusion

Caveolae, flask-shaped invaginations of cell membranes, are believed to play pivotal roles in transmembrane transportation of molecules and cellular signaling. Caveolin, a structural component of caveolae, interacts directly with G proteins and regulates their function. We investigated the effect of chronic β-adrenergic receptor stimulation on the expression of caveolin subtypes in mouse hearts by immunoblotting and Northern blotting. Caveolin-1 and -3 were abundantly expressed in the heart and skeletal muscles, but not in the brain. Continuous (−)-isoproterenol, but not (+)-isoproterenol, infusion via osmotic minipump (30 μg ⋅ g−1 ⋅ day−1) for 13 days significantly downregulated both caveolin subtypes in the heart. The expression of caveolin-1 was reduced by 48 ± 6.1% and that of caveolin-3 by 28 ± 4.0% ( P < 0.01, n = 8 for each). The subcellular distribution of caveolin subtypes in ventricular myocardium was not altered as determined by sucrose gradient fractionation. In contrast, the expression of both caveolin subtypes in skeletal muscles was not significantly changed. Our data suggest that the expression of caveolin subtypes is regulated by β-adrenergic receptor stimulation in the heart.

scholarly journals Adenylyl cyclase type 5 protein expression during cardiac development and stress

2009 ◽  
Vol 297 (5) ◽  
pp. H1776-H1782 ◽  
Author(s):  
Che-Lin Hu ◽  
Rachna Chandra ◽  
Hui Ge ◽  
Jayashree Pain ◽  
Lin Yan ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Adrenergic Receptor ◽  
Ventricular Hypertrophy ◽  
Cardiac Development ◽  
Mammalian Species ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Receptor Stimulation ◽  
Specific Antibodies ◽  
The Brain

Adenylyl cyclase (AC) types 5 and 6 (AC5 and AC6) are the two major AC isoforms expressed in the mammalian heart that mediate signals from β-adrenergic receptor stimulation. Because of the unavailability of isoform-specific antibodies, it is difficult to ascertain the expression levels of AC5 protein in the heart. Here we demonstrated the successful generation of an AC5 isoform-specific mouse monoclonal antibody and studied the expression of AC5 protein during cardiac development in different mammalian species. The specificity of the antibody was confirmed using heart and brain tissues from AC5 knockout mice and from transgenic mice overexpressing AC5. In mice, the AC5 protein was highest in the brain but was also detectable in all organs studied, including the heart, brain, lung, liver, stomach, kidney, skeletal muscle, and vascular tissues. Western blot analysis showed that AC5 was most abundant in the neonatal heart and declined to basal levels in the adult heart. AC5 protein increased in the heart with pressure-overload left ventricular hypertrophy. Thus this new AC5 antibody demonstrated that this AC isoform behaves similarly to fetal type genes, such as atrial natriuretic peptide; i.e., it declines with development and increases with pressure-overload hypertrophy.

Beta-receptor-mediated increase in cerebral blood flow during hypoglycemia

1987 ◽  
Vol 253 (4) ◽  
pp. H949-H955 ◽  
Author(s):  
B. R. Hollinger ◽  
R. M. Bryan
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Adrenergic Receptor ◽  
Regional Cerebral Blood ◽  
Receptor Stimulation ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Normoglycemic Control ◽  
The Brain ◽  
Oxide Anesthesia

We tested the hypothesis that beta-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin (15 U/kg); normoglycemic control rats were given saline. Propranolol (1.5 mg/kg) was administered to some control and some hypoglycemic rats to block the beta-adrenergic receptors. Regional CBF was measured using 4-[N-methyl-14C]iodoantipyrine. Plasma glucose in the normoglycemic and hypoglycemic groups was approximately 6 and 1.4 mumol/ml, respectively. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied from approximately 60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. We conclude that beta-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia.

scholarly journals Gi3 does not contribute to the inhibition of adenylate cyclase when stimulation of an α2-adrenergic receptor causes activation of both Gi2 and Gi3

1992 ◽  
Vol 284 (2) ◽  
pp. 565-568 ◽  
Author(s):  
S J McClue ◽  
E Selzer ◽  
M Freissmuth ◽  
G Milligan
Keyword(s):  
Adenylate Cyclase ◽  
G Proteins ◽  
Adrenergic Receptor ◽  
Genomic Dna ◽  
Gtpase Activity ◽  
Adrenergic Agonists ◽  
Dna Encoding ◽  
Receptor Stimulation ◽  
High Affinity ◽  
Stimulation Of

Agonist occupancy of the alpha 2-C10 adrenergic receptor in a stable clone (1C) of Rat 1 fibroblasts produced by transfection of cells with genomic DNA encoding this receptor causes the activation of both of the pertussis-toxin-sensitive G-proteins Gi2 and Gi3 [Milligan, Carr, Gould, Mullaney & Lavan (1991) J. Biol. Chem. 266, 6447-6455]. An IgG fraction from an antiserum (I3B) which identifies the C-terminal decapeptide of Gi3 alpha only was able to inhibit partially receptor stimulation of high-affinity GTPase activity. An equivalent fraction from an antiserum (AS7) able to identify the C-terminal decapeptide of Gi1 alpha + Gi2 alpha, but not Gi3 alpha, was also able to inhibit partially receptor stimulation of GTPase activity, and the effects of the two antisera were additive. By contrast, agonist-mediated inhibition of forskolin-amplified adenylate cyclase activity was abolished completely by the IgG fraction of antiserum AS7, but was not decreased by treatment with antiserum 13B. Based on the proportion of agonist-stimulated high-affinity GTPase which was prevented by each antiserum and on the measured membrane levels of Gi2 and Gi3, calculations indicated that essentially all of the cellular Gi3, but only 15% of the available Gi2, can be activated by the alpha 2-C10 adrenergic receptor in these cells. These results demonstrate that, although Gi3 is activated by alpha 2-adrenergic agonists in membranes of clone 1C cells, it does not contribute to the transduction of receptor-mediated inhibition of adenylate cyclase.

scholarly journals Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases

2021 ◽  
Vol 22 (13) ◽  
pp. 6858
Author(s):  
Fanny Gaudel ◽  
Gaëlle Guiraudie-Capraz ◽  
François Féron
Keyword(s):  
G Proteins ◽  
The Body ◽  
Trace Amines ◽  
Chemical Senses ◽  
Brain Areas ◽  
Genes Encoding ◽  
The Central Nervous System ◽  
Human Brains ◽  
The Brain ◽  
Brain Atlases

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

scholarly journals Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures

Epigenomes ◽  
2018 ◽  
Vol 2 (3) ◽  
pp. 13
Author(s):  
José Belizário
Keyword(s):  
Stem Cells ◽  
Skeletal Muscles ◽  
Small Population ◽  
Epigenetic Mechanisms ◽  
Cancer Risks ◽  
Mutational Signatures ◽  
Environmental Agents ◽  
Risk Of Malignancy ◽  
The Brain ◽  
Cellular Genome

Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting.

Translocation of G-Protein β3 subunit from the cytosol pool to the membrane pool by β1-Adrenergic receptor stimulation in perfused rat hearts

1999 ◽  
Vol 58 (9) ◽  
pp. 1497-1500 ◽  
Author(s):  
Ken Kageyama ◽  
Takeshi Murakami ◽  
Kenji Iizuka ◽  
Kumi Sato ◽  
Kazuo Ichihara ◽  
...  
Keyword(s):  
G Protein ◽  
Adrenergic Receptor ◽  
Receptor Stimulation ◽  
Rat Hearts ◽  
Perfused Rat Hearts

scholarly journals Low STAT3 expression sensitizes to toxic effects of β-adrenergic receptor stimulation in peripartum cardiomyopathy

2016 ◽  
pp. ehw086 ◽  
Author(s):  
Britta Stapel ◽  
Michael Kohlhaas ◽  
Melanie Ricke-Hoch ◽  
Arash Haghikia ◽  
Sergej Erschow ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Peripartum Cardiomyopathy ◽  
Toxic Effects ◽  
Receptor Stimulation
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