Effect of age on β-receptors, Gsα- and Giα-proteins in rat heart

Bazan, Ariane; Velde, E. Van de; Fraeyman, Norbert

doi:10.1016/0006-2952(94)90277-1

Cited by 26 publications

(7 citation statements)

References 36 publications

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“…This occurs by multiple mechanisms, including downregulation and decreased agonist binding of β1 receptors [40]. However, in rats, cardiac β receptor density does not change with age [41]. We observed significant downregulation of β1-adrenergic receptor protein, but β 2 -adrenergic receptors did not change.…”

Section: Discussionmentioning

confidence: 43%

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

et al. 2009

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Cardiac hypertrophy is frequently encountered in patients with renal failure and represents an independent risk factor for cardiovascular morbidity and mortality. The pathogenesis of cardiac hypertrophy is related to multiple factors, including excess adrenergic activity. This study investigated how renal injury in the early stages of life affects the adrenergic system and thereby potentially influences cardiac growth. Biomarkers of cardiac hypertrophy were used to assess adrenergic function. Newborn male Sprague-Dawley rats were allocated to three groups of five rats each: 5/6 nephrectomy (Nx), pair-fed controls (PF), and sham-operated (SH). Nx animals had significantly higher plasma urea nitrogen, serum creatinine, and mean arterial blood pressure. The heart-weight/body-weight ratio of the Nx cohort was higher than SH and PF (p < 0.001) groups. Plasma norepinephrine (NE) of Nx animals was almost twofold higher than SH and PF (p < 0.01) animals. Compared with SH and PF, Nx animals had higher alpha1A-receptor protein expression, lower cardiac beta1- and beta2-receptor protein expression (p < 0.05), but higher G-protein-coupled receptor kinase-2 (GRK2) expression (p < 0.05). Norepinephrine transporter protein (NET) and renalase protein expression in cardiac tissue from Nx pups were significantly lower than SH and PF. Our data suggest that early age Nx animals have increased circulating catecholamines due to decreased NE metabolism. Enhancement of cardiac GRK2 and NE can contribute to cardiac hypertrophy seen in Nx animals. Furthermore, AKT (activated via alpha1A receptors), as well as increased alpha1A receptors and their agonist NE, might contribute to the observed hypertrophy.

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Section: Discussionmentioning

confidence: 43%

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

et al. 2009

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Section: Ptx-sensitive G Proteins In Left Ventricular Membranesmentioning

confidence: 99%

“…Prior studies in rats had not provided a consensus as to the effects of age on cardiac G␣ i . There have been reports of increased G␣ i expression in Fisher 344 (21), Sprague-Dawley (19) and Wistar rats (25), as well as an increase in Fisher 344 G␣ i mRNA (22). However, there also have been reports of no change in G␣ i expression in Fisher 344 (22,23) and Wistar rats (6,26).…”

Section: Table Imentioning

confidence: 99%

“…In Sprague-Dawley rats, Bohm et al (19) found that age increases cardiac G␣ i , and the increase in G␣ i is reduced by exercise. In Wistar rats, Bazan et al (25) reported an increase in cardiac G␣ i with age, but Xiao et al (6) and Miyamoto et al (26) found no change. Some of the reported differences on the effect of age may be attributable to experimental design.…”

mentioning

confidence: 98%

“…These results are similar to other reports on ␤AR density in Fisher 344 rat hearts (21, 38 -42), though Mader et al (43) did report a decrease in affinity. In other rat strains there may be moderate decreases in receptor number (6,19,25,44).We also examined whether there are age-dependent changes in the ability of muscarinic receptors to inhibit ␤ 1 AR-and ␤ 2 AR-stimulated AC in rat ventricle. As shown in Table I, stimulation of muscarinic receptors strongly inhibits ␤AR-stimulated AC in both young and old rat hearts.…”

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confidence: 99%

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Age Increases Cardiac Gαi2 Expression, Resulting in Enhanced Coupling to G Protein-coupled Receptors

Kilts¹,

Akazawa²,

Richardson³

et al. 2002

Journal of Biological Chemistry

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Cardiac G protein-coupled receptors that function through stimulatory G protein G␣ s , such as ␤ 1 -and ␤ 2 -adrenergic receptors (␤ 1 ARs and ␤ 2 ARs), play a key role in cardiac contractility. Recent data indicate that several G␣ s -coupled receptors in heart also activate G␣ i , including ␤ 2 ARs (but not ␤ 1 ARs). Coupling of cardiac ␤ 2 ARs to G␣ i inhibits adenylyl cyclase and opposes ␤ 1 AR-mediated apoptosis. Dual coupling of ␤ 2 AR to both G␣ s and G␣ i is likely to alter ␤ 2 AR function in disease, such as congestive heart failure in which G␣ i levels are increased. Indeed, heart failure is characterized by reduced responsiveness of ␤ARs. Cardiac ␤AR-responsiveness is also decreased with aging. However, whether age increases cardiac G␣ i has been controversial, with some studies reporting an increase and others reporting no change. The present study examines G␣ i in left ventricular membranes from young and old Fisher 344 rats by employing a comprehensive battery of biochemical assays. Immunoblotting reveals significant increases with age in left ventricular G␣ i2 , but no changes in G␣ i3 , G␣ o , G␣ s , G␤ 1 , or G␤ 2 . Aging also increases ADP-ribosylation of pertussis toxin-sensitive G proteins. Consistent with these results, basal as well as receptor-mediated incorporation of photoaffinity label [ 32 P]azidoanilido-GTP indicates higher amounts of G␣ i2 in older left ventricular membranes. Moreover, both basal and receptor-mediated adenylyl cyclase activities are lower in left ventricular membranes from older rats, and disabling of G␣ i with pertussis toxin increases both basal and receptorstimulated adenylyl cyclase activity. Finally, age produces small but significant increases in muscarinic potency for the inhibition of both ␤ 1 AR-and ␤ 2 ARstimulated adenylyl cyclase activity. The present study establishes that G␣ i2 increases with age and provides data indicating that this increase dampens adenylyl cyclase activity.Cardiac contractility is controlled by several G protein-coupled receptors (GPCRs), 1 such as ␤ 1 -and ␤ 2 -adrenergic receptors (␤ 1 ARs and ␤ 2 ARs), that function through stimulatory GTP-binding regulatory proteins (G␣ s ) and activate adenylyl cyclase (AC). Activation of AC increases the formation of cAMP, which activates cAMP-dependent protein kinase A resulting in the phosphorylation of proteins controlling cardiac excitationcontraction (1). An important recent discovery is that ␤ 2 ARs (but not ␤ 1 ARs) in both rat (2, 3) and human heart (4) also activate G␣ i , a G␣-subunit that inhibits AC (5). We also demonstrated that G␣ i couples to several other G␣ s -coupled receptors in human heart, including receptors for histamine, glucagon, and serotonin (4). Coupling of ␤ 2 AR and other G␣ s -coupled receptors to G␣ i is relevant to cardiac function because inactivation of G␣ i by pertussis toxin (PTX) increases myocyte contractility in rat heart (6) and increases both basal and receptormediated AC activity in human heart (4). In addition to inhibiting AC, the G␣ i pathway in hea...

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Membrane‐bound and cytosolic forms of heterotrimeric G proteins in young and adult rat myocardium: Influence of neonatal hypo‐ and hyperthyroidism

Novotný

Bouřová²,

Kolář

et al. 2001

J of Cellular Biochemistry

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Membrane and cytosolic fractions prepared from ventricular myocardium of young (21-day-old) hypo- or hyperthyroid rats and adult (84-day-old) previously hypo- or hyperthyroid rats were analyzed by immunoblotting with specific anti-G-protein antibodies for the relative content of Gs alpha, Gi alpha/Go alpha, Gq alpha/G11 alpha, and G beta. All tested G protein subunits were present not only in myocardial membranes but were at least partially distributed in the cytosol, except for Go alpha2, and G11 alpha. Cytosolic forms of the individual G proteins represented about 5-60% of total cellular amounts of these proteins. The long (Gs alpha-L) isoform of Gs alpha prevailed over the short (Gs alpha-S) isoform in both crude myocardial membranes and cytosol. The Gs alpha-L/Gs alpha-S ratio in membranes as well as in cytosol increased during maturation due to a substantial increase in Gs alpha-L. Interestingly, whereas the amount of membrane-bound Gi alpha/Go alpha and Gq alpha/G11 alpha proteins tend to lower during postnatal development, cytosolic forms of these G proteins mostly rise. Neonatal hypothyroidism reduced the amount of myocardial Gs alpha and increased that of Gi alpha/Go alpha proteins. By contrast, neonatal hyperthyroidism increased expression of Gs alpha and decreased that of Gi alpha and G11 alpha in young myocardium. Changes in G protein content induced by neonatal hypo- and hyperthyroidism in young rat myocardium were restored in adulthood. Alterations in the membrane-cytosol balance of G protein subunits associated with maturation or induced by altered thyroid status indicate physiological importance of cytosolic forms of these proteins in the rat myocardium.

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Effect of age on β-receptors, Gsα- and Giα-proteins in rat heart

Cited by 26 publications

References 36 publications

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

Age Increases Cardiac Gαi2 Expression, Resulting in Enhanced Coupling to G Protein-coupled Receptors

Membrane‐bound and cytosolic forms of heterotrimeric G proteins in young and adult rat myocardium: Influence of neonatal hypo‐ and hyperthyroidism

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