Modification of cardiac adrenergic receptors by oxygen free radicals

1991 ◽  
Vol 260 (3) ◽  
pp. H821-H826 ◽  
Author(s):  
M. Kaneko ◽  
D. C. Chapman ◽  
P. K. Ganguly ◽  
R. E. Beamish ◽  
N. S. Dhalla
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Binding Sites ◽  
Adrenergic Receptors ◽  
Oxygen Free Radicals ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Alpha Adrenergic Receptors ◽  
Cgp 12177 ◽  
Number Of Binding Sites

To examine the effects of oxygen free radicals on alpha- and beta-adrenergic receptors, rat heart crude membranes were incubated with xanthine plus xanthine oxidase, H2O2, or H2O2 plus Fe2+. The assay of beta-adrenergic receptors involving [3H]dihydroalprenolol (DHA) binding revealed that the maximal number of binding sites (Bmax) and dissociation constant (Kd) were increased by xanthine plus xanthine oxidase. H2O2 increased the Kd value for [3H]DHA binding. When a hydrophilic ligand, [3H]CGP-12177, was used for the beta-adrenergic receptor assay, an increase in Kd value without any changes in Bmax value was evident on treating the membranes with xanthine plus xanthine oxidase. The assay of alpha-adrenergic receptors involving [3H]prazosin binding showed a decrease in the number of binding sites and an increase in Kd value only after a prolonged period of incubation. Both H2O2 and H2O2 plus Fe2+ increased the Kd value for [3H]prazosin without changes in Bmax. Changes in both alpha- and beta-adrenergic receptors similar to those with crude membranes were also seen by employing the purified heart sarcolemmal membranes. These data indicate that adrenergic receptors in the sarcolemmal membranes are modified by oxygen free radicals.

Baboon erythrocyte ghosts contain beta-adrenergic receptors

1985 ◽  
Vol 249 (1) ◽  
pp. C15-C19 ◽  
Author(s):  
E. E. Susanni ◽  
F. P. Ross ◽  
D. R. Scriven ◽  
C. Rosendorff
Keyword(s):  
Binding Sites ◽  
Adrenergic Receptors ◽  
Dependent Manner ◽  
Erythrocyte Ghosts ◽  
Beta Adrenergic Receptors ◽  
Concentration Dependent Manner ◽  
Apparent Dissociation Constant ◽  
Beta Adrenergic ◽  
Adrenergic Antagonist ◽  
Number Of Binding Sites

We have used the beta-adrenergic antagonist [3H]dihydroalprenolol [( 3H]DHA) to identify binding sites on the erythrocyte membrane of the primate Papio ursinus. Analysis of the saturation isotherm revealed binding to be saturable with a maximal number of binding sites of 499 fmol/mg protein. [3H]DHA binds specifically to the erythrocyte ghosts with an apparent dissociation constant (Kd) of 0.57 +/- 0.06 nM. A similar value for Kd (0.46 +/- 0.07 nM) was evaluated from the rate constants of association (0.013 +/- 0.003 X nM-1 X min-1) and dissociation (0.006 +/- 0.001 X min-1). beta-adrenergic agonists compete for the binding sites with an order of potency (dl-isoproterenol greater than l-epinephrine greater than l-norepinephrine) typical of a beta 2-adrenergic receptor. Binding was shown to be stereospecific with l-stereoisomers being more potent than their corresponding d-stereoisomers in causing half-maximal inhibition. Isoproterenol stimulated the production of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) in a concentration-dependent manner, maximal levels (1.130 +/- 0.358 pmol cAMP/10(8) cells) being four times the basal levels. The results demonstrate the existence of a large number of beta-adrenergic receptors on baboon erythrocyte ghosts.

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.

Effects of some autonomic drugs on duodenal smooth muscle.

1979 ◽  
Vol 236 (1) ◽  
pp. E33
Author(s):  
S Anuras ◽  
D L Faulk ◽  
J Christensen
Keyword(s):  
Smooth Muscle ◽  
Adrenergic Receptors ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Adrenergic Agonists ◽  
Beta Adrenergic Receptors ◽  
Cholinergic Agonists ◽  
Beta Adrenergic ◽  
Alpha Adrenergic Receptors ◽  
Relative Potencies

Longitudinal muscle strips (LMS) and circular muscle strips (CMS), 2 mm wide and 1.5--2 cm long, from opossum duodenum were exposed to some autonomic agonists. The cholinergic agonists, acetylcholine, carbachol, methacholine, and bethanechol stimulated only tonic contractions in LMS and tonic followed by phasic contractions in CMS. These effects were abolished by atropine 10(-6) M. The ED50S of all cholinergic agonists for LMS were significantly lower than for CMS. Norepinephrine caused initial contraction (abolished by phenoxybenzamine, 10(-4) M), followed by relaxation (abolished by propranolol, 10(-5) M), and isopropylnorepinephrine caused relaxation (abolished by propranolol, 10(-5) M) in both layers. There were no differences in relative potencies for adrenergic agonists between the layers. Tetrodotoxin did not affect the response to adrenergic agonists. Thus, the potency of cholinergic agonists is greater in longitudinal than in circular muscle, and the layers respond differently to cholinergic agonists. The alpha-adrenergic receptors mediate contraction and beta-adrenergic receptors mediate relaxation on the duodenal smooth muscle.

Adrenergic and local control of O2 uptake during and after severe hypoxia

1986 ◽  
Vol 61 (5) ◽  
pp. 1920-1927 ◽  
Author(s):  
C. E. King ◽  
S. M. Cain
Keyword(s):  
Adrenergic Receptors ◽  
Regional Distribution ◽  
Severe Hypoxia ◽  
Whole Body ◽  
Beta Adrenergic Receptors ◽  
O2 Uptake ◽  
Beta Adrenergic ◽  
Alpha Adrenergic Receptors ◽  
O2 Delivery ◽  
O2 Deficit

The distribution of whole-body O2 supply during severe hypoxia and recovery and its relation to the regional distribution of O2 deficit and repayment was studied. Mongrel dogs were anesthetized, paralyzed, and ventilated to maintain an end-tidal PCO2 between 35 and 40 Torr. In one group, the alpha- and beta-adrenergic receptors were blocked to eliminate neural and humoral adrenergic influences. In a second group, alpha-adrenergic receptors were stimulated to decrease O2 delivery by excessive vasoconstriction. In a third group, beta-adrenergic receptors were stimulated to increase O2 delivery. Whole-body and hindlimb muscle O2 uptake and vascular responses were measured during normoxic control, 15 or 30 min of severe hypoxia (9% O2 in N2), and 20 or 30 min of normoxic recovery, respectively. The whole-body O2 deficit and excess O2 uptake in recovery were partitioned into muscle and nonmuscle areas. The data showed that neural or humoral influences had little effect on the regional distribution of the total O2 deficit and O2 excess in recovery. The O2 deficit could be decreased somewhat by increasing delivery, but the amount of excess O2 used in recovery was unaffected. This suggested that the excess O2 use in recovery was more a function of an energy deficit during hypoxia and not an O2 deficit.

Effect of insulin on adipocyte lipolysis in exercise-trained rats

1993 ◽  
Vol 74 (6) ◽  
pp. 2935-2939 ◽  
Author(s):  
K. Suda ◽  
T. Izawa ◽  
T. Komabayashi ◽  
M. Tsuboi ◽  
S. Era
Keyword(s):  
Exercise Training ◽  
Adrenergic Receptors ◽  
Insulin Dose ◽  
Displacement Rate ◽  
Control Group ◽  
Trained Group ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Low Concentrations ◽  
Cgp 12177

The effect of exercise training on the antilipolytic action of insulin was studied in rat adipocytes. Exercise training enhanced lipolysis induced by norepinephrine. Insulin dose dependently inhibited norepinephrine- (1 microM) stimulated lipolysis in both groups. Its inhibition rate was significantly greater in the trained than in the control group. Thus, exercise training enhanced the antilipolytic action of insulin. In the control group, insulin (1,000 microU/ml) reduced the displacement rate of [3H]CGP-12177 binding to adipocytes by low concentrations of (-)-norepinephrine. The slope factor without insulin was 0.76, whereas that with insulin was 0.95. In the trained group, insulin did not affect the competition binding of (-)-norepinephrine for [3H]CGP-12177. The displacement rate of [3H]CGP-12177 binding from adipocytes by low concentrations of (-)-norepinephrine was significantly greater in the trained than in the control group. The number of surface beta-adrenergic receptors per adipocyte was smaller in the trained than in the control group. Cilostamide, which blocks the antilipolytic action of insulin, restored lipolysis in both groups. The recovery rate was significantly greater in the trained than in the control group. These findings suggest that the enhanced antilipolytic action by insulin in the trained group occurs at a site distal to the binding of norepinephrine to beta-adrenergic receptors and that it is due to the increased activity of particulate low-Michaelis constant phosphodiesterase.

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.

Differences in affinity of cardiac beta-adrenergic receptors for [3H]dihydroalprenolol

1986 ◽  
Vol 250 (3) ◽  
pp. H490-H497
Author(s):  
K. H. Muntz ◽  
T. A. Calianos ◽  
D. T. Vandermolen ◽  
J. T. Willerson ◽  
L. M. Buja
Keyword(s):  
Cardiac Myocytes ◽  
Adrenergic Receptors ◽  
Dissociation Constants ◽  
Specific Binding ◽  
Scatchard Analysis ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Number Of Binding Sites ◽  
Tissue Compartments

We performed quantitative light microscopic autoradiography of [3H]dihydroalprenolol (DHA) binding to frozen sections of canine myocardium to test the hypothesis that there are differences in the density or affinity of beta-adrenergic receptors on various tissue compartments. In one study, with concentrations of [3H]DHA from 0.34 to 5.1 nM, specific binding to cardiac myocytes was saturable, whereas nonspecific binding was linear with ligand concentration. Arterioles had more specific grain counts than muscle cells (P less than 0.0001), and Scatchard analysis showed that the arterioles had a much higher affinity for [3H]DHA than myocytes. In a second study with lower concentrations of [3H]DHA (0.19-1.98 nM), binding to the arterioles saturated, whereas binding to the cardiac myocytes did not. Specific binding to arterioles was significantly higher (P less than 0.0001) than binding to myocytes at all concentrations of [3H]DHA. The dissociation constants for the subendocardial and subepicardial myocytes were 1.57 and 1.71 nM, respectively, while the dissociation constant for the arterioles was 0.26 nM. The maximum number of binding sites was 911 grains/0.9 X 10(-2) mm2 for subepicardial myocytes, 936 for subendocardial myocytes, and 986 for arterioles. The large nerves accompanying an epicardial artery also demonstrated specific [3H]DHA binding. Thus this study has demonstrated major differences in the distribution and affinity of beta-adrenergic receptors, which may help to explain various physiological responses to beta-adrenergic stimulation.

Increased beta-adrenergic receptors in brown fat of winter-acclimatized Alaskan voles

1983 ◽  
Vol 245 (3) ◽  
pp. R357-R363 ◽  
Author(s):  
D. D. Feist
Keyword(s):  
Cold Acclimation ◽  
Binding Sites ◽  
Adrenergic Receptors ◽  
Specific Binding ◽  
Brown Fat ◽  
Scatchard Analysis ◽  
Beta Adrenergic Receptors ◽  
Hormonal Stimulation ◽  
Beta Adrenergic ◽  
Specific Binding Sites

To assess a possible mechanism for the enhanced thermogenesis of cold-acclimated and winter-acclimatized red-backed voles (Clethrionomys rutilus), beta-adrenergic receptors of brown fat were characterized by specific binding of (-)-[3H]-dihydroalprenolol [( 3H]DHA) to isolated brown fat membranes from 23 degrees C-acclimated controls, cold-acclimated (5 wk or 5 mo at 5 degrees C), wild summer, and winter-acclimatized voles. Scatchard analysis to determine the equilibrium dissociation constant (Kd) and the maximum number of binding sites (Bmax) for control brown fat membranes gave a Kd of 4.45 nM [3H]DHA and Bmax of 249 fmol [3H]DHA bound per milligram of protein. beta-Adrenergic agonists competed for specific binding sites with an order of potency typical of the beta 1 subtype of adrenergic receptors: (-)-isoproterenol greater than (-)-norepinephrine greater than or equal to (-)-epinephrine. After cold acclimation for 5 wk or 5 mo, the Kd and Bmax for adrenergic binding sites were similar to those of controls. Brown fat mass was 1.5 times greater than that of controls after 5 wk cold acclimation but similar to controls after 5 mo cold acclimation. Winter voles had 1.7 times higher Bmax and 1.6 times more brown fat than summer voles. Thus seasonal acclimatization to winter in red-backed voles appears to involve an increase in beta-adrenergic receptors in brown fat, but cold acclimation does not. The results suggest quantitative and possibly qualitative differences in neural and hormonal stimulation of brown fat between cold acclimation and winter acclimatization in voles.

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