Effects of coronary arterial reperfusion on beta-adrenergic receptor-adenylyl cyclase coupling

1993 ◽  
Vol 264 (1) ◽  
pp. H196-H204 ◽  
Author(s):  
D. E. Vatner ◽  
K. Kiuchi ◽  
W. T. Manders ◽  
S. F. Vatner
Keyword(s):  
Adenylyl Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Adenylyl Cyclase Activity ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
High Affinity

The effects of 1 h of coronary arterial occlusion (CAO) followed by 15 min reperfusion (CAR) were examined in nine conscious dogs. Ischemia was verified by decreased regional blood flow (radioactive microspheres) and loss of systolic regional wall motion in the ischemic zone. beta-Adrenergic receptor density assessed by 125I-labeled cyanopindolol binding in a crude membrane fraction tended to decrease but was not significantly different. However, adenylyl cyclase activity and the guanine nucleotide stimulatory protein (Gs) were reduced in ischemic subendocardium compared with nonischemic subendocardium. The fraction of beta-adrenergic receptors binding agonist with high affinity increased in ischemic subendocardial and subepicardial layers. Compared with prior data in experiments with 1 h CAO without CAR, the increase in beta-adrenergic receptor density that occurs with myocardial ischemia is rapidly reversed with CAR of 15 min duration, while the decreased fraction of receptors binding agonist with high affinity was reversed to an increase in high-affinity receptors. The global decreases in adenylyl cyclase and Gs, which have been observed with simple CAO, persist but are observed selectively in the previously ischemic subendocardium after CAR. Thus both CAO and CAR affect beta-adrenergic receptors and adenylyl cyclase differently. During CAR, increased numbers of beta-adrenergic receptors binding agonist with high affinity occur potentially as a compensatory mechanism in the face of persistent reductions in adenylyl cyclase activity and Gs.

Beta-receptors and adenylate cyclase: comparison of nonischemic, ischemic, and postmortem tissue

1990 ◽  
Vol 258 (1) ◽  
pp. H140-H144 ◽  
Author(s):  
D. E. Vatner ◽  
M. A. Young ◽  
D. R. Knight ◽  
S. F. Vatner
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Striking Similarity ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic

We compared the effects of myocardial ischemia and postmortem changes on beta-adrenergic receptors and their coupling to adenylate cyclase activity. The effects of 1 h of left circumflex coronary artery occlusion were examined in eight conscious calves, which were then anesthetized with pentobarbital sodium, and the left ventricle was divided into nonischemic and ischemic regions. A crude membrane fraction was prepared from each region and from the nonischemic tissue 1 h postmortem. beta-Adrenergic receptor density increased (152 +/- 55%) and decreases in basal (-21 +/- 6.1%), isoproterenol-stimulated (-25 +/- 8.0%), 5'-guanylylimidodiphosphate [Gpp(NH)p]-stimulated (-17 +/- 5.8%), fluoride-stimulated (-26 +/- 5.8%), and forskolin-stimulated (-31 +/- 8.4%) adenylate cyclase activities were observed in the ischemic myocardium compared with nonischemic myocardium. Similarly, in postmortem samples, beta-adrenergic receptor density rose 58 +/- 16%, whereas decreases in basal (-48 +/- 8.7%), isoproterenol-stimulated (-61 +/- 7.8%), Gpp(NH)p-stimulated (-58 +/- 7.0%), fluoride-stimulated (-64 +/- 6.1%), and forskolin-stimulated (-52 +/- 6.2%) adenylate cyclase activities were observed. Agonist-binding competition curves with isoproterenol were shifted, indicating that beta-adrenergic receptors were binding agonists with low affinity in both the ischemic and postmortem myocardium. The marked, but directionally opposite, changes in receptor density and adenylate cyclase that occur postmortem indicate the importance of prompt processing of tissues. The striking similarity in response of beta-adrenergic receptor agonist and antagonist binding and adenylate cyclase activity in ischemic and postmortem tissue raises the speculation that similar mechanisms may operate under both conditions.

Effect of age and hypoxia on beta-adrenergic receptors in rat heart

1991 ◽  
Vol 71 (6) ◽  
pp. 2094-2098 ◽  
Author(s):  
S. L. Mader ◽  
C. L. Downing ◽  
E. Van Lunteren
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Left Ventricular ◽  
Hypoxic Exposure ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Young Rats ◽  
Age Related

Previous reports suggest that hypoxia downregulates cardiac beta-adrenergic receptors from young rats. Because aging alters response to stress, we hypothesized an age-related alteration in the response to hypoxia. Male Fischer-344 rats, aged 3 and 20 mo, were divided into control and hypoxic groups. The hypoxic rats were exposed to hypobaric hypoxia (0.5 atm) for 3 wk. After hypoxic exposure, body weight decreased, hematocrit increased, right ventricular weight increased, and left ventricular weight decreased in all animals. beta-Adrenergic receptor density declined after hypoxic exposure in the young but not in the older animals, a change that was confined to the left ventricle. beta-Adrenergic receptor density in the right ventricle was significantly lower in the older animals than in the young animals. Plasma catecholamines (norepinephrine, epinephrine) drawn after the animals were killed (stress levels) decreased in young rats and increased in old rats after the exposure to hypoxia. Hypoxia is a useful physiological stress that elucidates age-related changes in cardiac beta-adrenergic receptor and catecholamine regulation that have not previously been described.

TNF-alpha inhibits isoproterenol-stimulated adenylyl cyclase activity in cultured airway smooth muscle cells

1997 ◽  
Vol 272 (4) ◽  
pp. L644-L650 ◽  
Author(s):  
C. W. Emala ◽  
J. Kuhl ◽  
C. L. Hungerford ◽  
C. A. Hirshman
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Adenylyl Cyclase ◽  
Airway Smooth Muscle ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Tnf Alpha ◽  
Adenylyl Cyclase Activity ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic

Inflammation, increased cytokine production, and decreased responsiveness of airway smooth muscle (ASM) to beta-adrenergic agonists are characteristics of asthma. We questioned whether the cytokine tumor necrosis factor-alpha (TNF-alpha) directly impaired beta-adrenergic signal transduction in cultured canine ASM cells. Confluent ASM cells exposed to TNF-alpha (0.1-10 ng/ml) for 72 h showed lower maximal levels of adenylyl cyclase activity in response to isoproterenol (10 ng/ml; 14 +/- 4.3 vs. 7.5 +/- 1.3 pmol adenosine 3',5'-cyclic monophosphate x well(-1) x 20 min(-1), control vs. treated, respectively), despite no changes in beta-adrenergic receptor numbers (maximum number of binding sites = 4.8 +/- 0.72 vs. 4.5 +/- 0.81 fmol/mg protein, control vs. treated, respectively). Adenylyl cyclase activities in response to prostaglandin E1, NaF, or forskolin were not different in treated and untreated cells. These results demonstrate that a cytokine known to be increased during exacerbation of asthmatic symptoms directly impairs beta-adrenergic function in ASM cells and suggests a mechanism by which inflammation impairs beta-adrenergic receptor signal transduction in asthma.

Liver beta-adrenergic receptors, G proteins, and adenylyl cyclase activity in obesity-diabetes syndromes

1994 ◽  
Vol 266 (6) ◽  
pp. C1664-C1672 ◽  
Author(s):  
N. Begin-Heick
Keyword(s):  
Adenylyl Cyclase ◽  
G Proteins ◽  
Binding Sites ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Adenylyl Cyclase Activity ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Obesity And Diabetes ◽  
Liver Membranes

The ob and db genes produce similar hormonal anomalies in mice. Although the expression of the syndromes diverges with age, at 8-12 wk both ob/ob and db/db mice are hyperglycemic and hyperinsulinemic and show evidence of hypercorticoidism. Nevertheless, membranes isolated from livers of ob/ob and db/db mice behave differently in terms of adenylyl cyclase activity and beta-adrenergic receptor function. There are three times as many beta 2-adrenergic receptor binding sites and a threefold increase in the response to catecholamines in ob/ob mouse liver membranes than in comparable preparations from normal controls or db/db mice. By contrast, the two main G proteins of liver membranes (Gs alpha and Gi alpha 2) are less abundant in the mutants, ob/ob and db/db, than in their respective lean controls. Adrenalectomy normalizes the exaggerated response to beta-adrenergic agonists and the number of beta-adrenergic binding sites in the ob/ob mouse. This shows that the enhanced beta-adrenergic receptor response is linked to hypercorticoidism. Cellular maturation and differentiation (D. C. Watkins, J. K. Northrup, and C. C. Malbon, J. Biol. Chem. 262: 10651-10657, 1987) and diseases such as obesity and diabetes (cf. N. McFarlane-Anderson, J. Bailly, and N. Begin-Heick, Biochem. J. 282: 15-23, 1992) have been associated with modifications in the complement of G proteins detected in cells. However, the relationship among levels, types, and intracellular localization of G proteins in tissues and their influence on the transduction of the message to an effector system, such as adenylyl cyclase, are not yet well understood.

scholarly journals Thyroid-hormone modulation of the number of β-adrenergic receptors in rat fat-cell membranes

1978 ◽  
Vol 176 (3) ◽  
pp. 1007-1010 ◽  
Author(s):  
Y Giudicelli
Keyword(s):  
Thyroid Hormone ◽  
Binding Sites ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Fat Cell ◽  
Beta Adrenergic ◽  
Hormone Modulation ◽  
Β Adrenergic Receptors

Adipocytes from thyroidectomized rats contain 3 times less [3H]dihydroalprenolol-binding sites (beta-adrenergic receptors) than adipocytes from euthyroid animals. This alteration is not solely due to cell-size differences, but also to a thyroidectomy-induced defect in beta-adrenergic receptor density per adipocyte surface area, a defect that is furthermore corrected by tri-iodothyronine treatment.

Hepatic sexual dimorphism: ontogeny and influence of adult gonadectomy

1989 ◽  
Vol 256 (3) ◽  
pp. E392-E400
Author(s):  
R. K. Studer ◽  
L. Ganas
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Female Rats ◽  
Adenylate Cyclase System ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Intact Cells ◽  
Beta Adrenergic ◽  
Receptor Concentration ◽  
Males And Females

The ontogeny of alpha 1- and beta-adrenergic receptors and their relative stimulation of phosphorylase alpha activity in hepatic tissue from male and female rats were compared. A decrease in beta-adrenergic receptor concentration and 4-(t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one HCl affinity for these sites was found in males and females, when data from membranes of 20- to 22-day animals was compared with that from neonates. No subsequent decline in receptor concentration was noted in the female; however, the beta-mediated phosphorylase activation was further diminished by 49-56 days, suggesting maturational changes beyond the receptor-adenylate cyclase system. Although high-affinity beta-adrenergic receptors were documented in membranes from pubertal males, they were not identified on the intact cells, and activation of phosphorylase alpha via the beta-pathway was minimal. This suggests the majority of the beta-receptors are sequestered in cellular sites not accessible to the hydrophilic ligand or epinephrine in the sexually mature male. Ontogeny of the alpha 1-adrenergic receptors was similar in males and females. Gonadectomy of mature males and females did not eliminate the sexual differences in adrenergic response. However, the ovariectomized females developed an enhanced basal and alpha-adrenergic stimulated phosphorylase activity. The rise in cytosolic free calcium in response to epinephrine was increased in the ovariectomized females to values seen in the intact male, whereas the response in the castrate male was depressed. The results suggest the dimorphism in alpha 1- and beta-adrenergic receptor function is determined by factors other than the ambient concentration of sex steroids in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hypoxia on density of beta-adrenergic receptors

1981 ◽  
Vol 50 (2) ◽  
pp. 363-366 ◽  
Author(s):  
N. F. Voelkel ◽  
L. Hegstrand ◽  
J. T. Reeves ◽  
I. F. McMurty ◽  
P. B. Molinoff
Keyword(s):  
High Altitude ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Low Dose ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Altitude Exposure

Exposure to chronic hypoxia results in a lower resting heart rate and a blunted cardiovascular responsiveness to beta-adrenergic receptor stimulation. Possible effects of acclimatization to high altitude on the binding of [125I]iodohydroxybenzylpindolol to beta-adrenergic receptors on membranes of right and left ventricles of rat heart were determined. Chronic high-altitude exposure led to a decrease in the density of beta-adrenergic receptors in nonhypertrophied left ventricles as well as in hypertrophied right ventricles. The affinity of the receptor for the radioligand was not changed by the exposure to high altitude, suggesting that the properties of the receptor were not affected. Basal and isoproterenol-stimulated adenylate cyclase activities were decreased in membranes prepared from hearts and pulmonary arteries of rats acclimatized to high altitude. The loss of cardiac beta-adrenergic receptors in rats adapted to high altitude was prevented by the chronic coadministration of a low dose of DL-propranolol. The results suggest that changes in beta-adrenergic receptor density may partially explain the hemodynamic adaptation that occurs with chronic hypoxia. These decreases may be due to a loss of functional beta-adrenergic receptors caused by chronically elevated concentrations of circulating neurally released catecholamines.

Characterization of beta-adrenergic receptors in cultured bovine tracheal gland cells

1989 ◽  
Vol 256 (2) ◽  
pp. C310-C314 ◽  
Author(s):  
J. M. Madison ◽  
C. B. Basbaum ◽  
J. K. Brown ◽  
W. E. Finkbeiner
Keyword(s):  
Binding Sites ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Rank Order ◽  
Beta Adrenergic Receptors ◽  
Binding Studies ◽  
Beta Adrenergic ◽  
High Affinity ◽  
Gland Cells ◽  
Beta 2

We characterized the beta-adrenergic receptors that mediate secretory responses to isoproterenol in cultured bovine tracheal submucosal gland cells. Previous studies have shown that these cells have morphological and biochemical features characteristic of serous cells. Isoproterenol, epinephrine, and norepinephrine each stimulated the secretion of 35SO4-labeled macromolecules from these cultured serous cells with a rank order of potency (isoproterenol greater than epinephrine greater than norepinephrine) consistent with the presence of beta 2-adrenergic receptors. These functional studies were supported by radioligand-binding studies using [I125]-iodocyanopindolol (125I-CYP) to identify beta-adrenergic receptors. 125I-CYP binding to membrane particulates prepared from cultured serous cells was saturable and of high affinity (equilibrium dissociation constant 20 +/- 3 pM; mean +/- SE, n = 6) and was antagonized stereoselectively by propranolol. Adrenergic agonists competed for 125I-CYP-binding sites with a rank order of potency characteristic of the beta 2-adrenergic receptor subtype. A specific beta 2-adrenergic receptor antagonist, ICI 118.551, competed for a single class of 125I-CYP-binding sites with high affinity (inhibition constant 1.8 +/- 0.3 nM, n = 3). We concluded that the secretory response of cultured tracheal gland cells to isoproterenol is a response mediated by beta-adrenergic receptors of the beta 2 subtype.

Refined membrane preparations mask ischemic fall in myocardial beta-receptor density

1989 ◽  
Vol 257 (3) ◽  
pp. H1032-H1036
Author(s):  
A. A. Wolff ◽  
D. K. Hines ◽  
J. S. Karliner
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Coronary Occlusion ◽  
Acute Ischemia ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Use Of Data ◽  
H2 Receptors ◽  
Myocardial Membrane

Most of the previous studies of ischemic myocardial beta-adrenergic receptors have employed membrane preparations in which the initial pellet from the myocardial homogenate spun at a low speed was discarded. We studied changes in beta-adrenergic receptor density ([125I]-iodocyanopindolol; Bmax) during 30 min of coronary occlusion in surgically anesthetized open-chest rabbits using just such a pellet [homogenized heart spun at 1,000 g (1,000-g pellet)], as well as a second pellet from the supernatant of the first pellet [spun at 40,000 g (40,000-g pellet)]. Bmax fell during acute ischemia in the 1,000-g pellet [46.8 +/- 6.1 vs. 21.6 +/- 2.4 (SE) fmol/mg protein; P less than 0.01; n = 7] but did not change in the 40,000-g pellet [46.8 +/- 6.5 vs. 47.9 +/- 2.6 (SE) fmol/mg protein; P = NS; n = 6]. The 1,000-g pellet contained 70.0 +/- 8.1% of the beta-adrenergic receptors measured between the two preparations (P less than 0.05; n = 8) and all of the histamine H2-receptors; therefore, to minimize receptor loss and other potential artifacts, unspun myocardial homogenate was studied. An ischemic decrease in Bmax was still observed [32.9 +/- 2.0 vs. 20.9 +/- 4.1 (SE) fmol/mg protein; P less than 0.05; n = 5]. These results support the use of data from cruder myocardial membrane preparations (e.g., 1,000-g pellet or unspun homogenate), which may be of greater pathophysiological relevance than data derived from a standard more-refined preparation (40,000-g pellet).

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