Human tissue adrenergic receptors are not predictive of responses to epinephrine in vivo

1989 ◽  
Vol 256 (5) ◽  
pp. E600-E609
Author(s):  
S. B. Liggett ◽  
S. D. Shah ◽  
P. E. Cryer
Keyword(s):  
Skeletal Muscle ◽  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Interindividual Variation ◽  
Mononuclear Leukocytes ◽  
Circulating Cells ◽  
Beta 2 ◽  
Sufficient Magnitude

To test the hypotheses that adrenergic receptor and adenylate cyclase characteristics of easily accessible circulating cells reflect those of relatively inaccessible extravascular catecholamine target tissues in a subtype-specific fashion and that these characteristics predict responses to catecholamines in vivo, we studied 22 normal humans. Adrenergic receptors and their linked adenylate cyclase systems were measured in mononuclear leukocytes (MNL; beta 2), platelets (alpha 2), skeletal muscle membranes (beta 2), and fat cells (B1 and alpha 2) and compared with the responses to stepped, intravenous epinephrine infusions in vivo. MNL beta 2-adrenergic receptor densities (but not antagonist affinities) were correlated (r = 0.627; P less than 0.01) with skeletal muscle beta 2-adrenergic densities. However, other adrenergic receptor characteristics and basal and maximally stimulated adenosine 3',5'-cyclic monophosphate (cAMP) contents of MNL and all adrenergic receptor characteristics and cAMP contents of platelets were unrelated to the corresponding measurements in skeletal muscle and fat. Furthermore, there were no consistent relationships between tissue adrenergic receptor-adenylate cyclase characteristics and the chronotropic, diastolic depressor, lipolytic, ketogenic, glycemic, or glycogenolytic-glycolytic responses to epinephrine in vivo. Thus the data support the hypothesis that adrenergic receptor densities on circulating cells reflect those of extravascular target tissues in a subtype-specific fashion. On the other hand, the data do not support the hypothesis that physiological interindividual variation of adrenergic receptor characteristics is of sufficient magnitude to alter sensitivity to epinephrine in vivo.

beta-Adrenergic receptors in the developing rabbit lung

1981 ◽  
Vol 240 (4) ◽  
pp. E351-E357 ◽  
Author(s):  
J. A. Whitsett ◽  
M. A. Manton ◽  
C. Darovec-Beckerman ◽  
K. G. Adams ◽  
J. J. Moore
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Receptor Subtypes ◽  
Beta Adrenergic Receptors ◽  
Rabbit Lung ◽  
Beta Adrenergic ◽  
Beta 2

beta-Adrenergic receptors and catecholamine-sensitive adenylate cyclase were identified and partially characterized in membrane fractions of rabbit lungs from day 25 of gestation to adulthood with the beta-adrenergic antagonists (--)-[3H]dihydroalprenolol [(--)-[3H]DHA] and (--)-[125I]iodohydroxybenzylpindolol [(--)-[125I]HYP]. beta-Adrenergic receptor number (Bmax) increased 11.5-fold during this time period, increasing progressively during the latter days of gestation and the early neonatal period, from 37 +/- 10 fmol/mg protein at 25 days gestation to 425 +/- 51 fmol/mg in the adult rabbit lung (mean +/- SD). Receptor affinity for (--)-[3H]DHA (KD = 1.8 nM) or (--)-[125I]HYP (KD - 0.104 nM) and the proportion of beta 1- and beta 2-adrenergic receptor subtypes (60% beta 1 and 40% beta 2) did not change with advancing age. Basal adenylate cyclase activity in lung homogenates decreased significantly with increasing age, whereas the activity in the presence of catecholamine or NaF remained nearly constant. Catecholamines stimulated adenylate cyclase activity at all ages studied supporting a role of the maturation of beta-adrenergic receptors in the regulation of pulmonary function.

Regulation of Norepinephrine Release by β2-Adrenergic Receptors during Halothane Anesthesia

1995 ◽  
Vol 82 (6) ◽  
pp. 1417-1425. ◽  
Author(s):  
Robert Deegan ◽  
Huai Bing He ◽  
Yuri Krivoruk ◽  
Alastair Wood ◽  
Margaret Wood
Keyword(s):  
Blood Flow ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Hind Limb ◽  
Femoral Vein ◽  
Presynaptic Receptors ◽  
Limb Blood Flow ◽  
Halothane Anesthesia ◽  
Beta 2

Background Presynaptic receptors control norepinephrine (NE) release. It has been hypothesized that epinephrine stimulates prejunctional beta 2-adrenergic receptors to facilitate NE release from sympathetic nerve endings, and therefore, presynaptic receptors controlling NE release are potential therapeutic targets to limit the adverse effects of excess sympathetic stimulation during anesthesia. We have previously demonstrated beta 2-adrenergic receptor-augmented release of NE in the human forearm and have shown that halothane inhibits sympathetic activity in vivo by decreasing the NE spillover rate into plasma. The goal of the current study was to determine the effect of halothane on beta 2-adrenergic receptor-augmented NE release in a canine hind-limb experimental model. Methods Seven female dogs were studied awake and during halothane anesthesia (1.0 minimum alveolar concentration). A trace dosage of [3H]NE (15 microCi over a 1-min period and 0.6 microCi/min thereafter) was infused into the femoral vein. Before and during femoral arterial administration of isoproterenol at two dosages (30 and 80 mg/min), hind-limb blood flow was measured by an ultrasonic flow probe and hind-limb NE spillover by an isotope dilutional technique. Results In awake dogs, isoproterenol significantly increased hind-limb blood flow and NE spillover into the hind limb. Halothane had no effect on baseline or isoproterenol-stimulated hind-limb blood flow (a postjunctional beta 2 effect) but significantly inhibited the isoproterenol-induced increase in hind-limb NE spillover (a prejunctional beta 2 effect). Conclusions The isoproterenol-mediated increase in NE release is inhibited by halothane anesthesia, indicating that halothane inhibits prejunctional beta 2-adrenergic receptor regulation of NE release.

scholarly journals Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors.

1993 ◽  
Vol 268 (5) ◽  
pp. 3201-3208
Author(s):  
S. Pippig ◽  
S. Andexinger ◽  
K. Daniel ◽  
M. Puzicha ◽  
M.G. Caron ◽  
...  
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Kinase ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Beta 2

scholarly journals Autoradiographic visualization of beta-adrenergic receptors in normal and denervated skeletal muscle.

1979 ◽  
Vol 27 (10) ◽  
pp. 1308-1311 ◽  
Author(s):  
B Lavenstein ◽  
W K Engel ◽  
N B Reddy ◽  
S Carroll
Keyword(s):  
Skeletal Muscle ◽  
Blood Vessels ◽  
Adrenergic Receptors ◽  
Cellular Localization ◽  
Muscle Fibers ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Adrenergic Blocker

Autoradiographic localization of beta-adrenergic receptors in rat skeletal muscle in vivo was achieved utilizing [125I]-iodohydroxybenzylpindolol, a potent beta-adrenergic blocker with high affinity and specificity for those receptors. In normal muscle the beta-adrenergic receptors were localized mainly to blood vessels, arterioles greater than venules, with much less concentration of grains over the fascicles of muscle fibers. One week after denervation there was an increase in binding both to blood vessels and muscle fibers, more so in soleus and gactrocnemius than in extensor digitorum longus. While these results parallel in vitro biochemical studies, they dictate caution when inferring cellular localization of beta-adrenergic receptors (and other molecules) solely on the basis of biochemical techniques applied to subcellular fractions of whole-organ homogenates.

Cardiovascular effects of dobutamine during exercise in dogs

1989 ◽  
Vol 257 (3) ◽  
pp. H954-H960
Author(s):  
G. C. Haidet ◽  
T. I. Musch ◽  
D. B. Friedman ◽  
G. A. Ordway
Keyword(s):  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Maximal Exercise ◽  
Cardiovascular Effects ◽  
Receptor Reserve ◽  
Concomitant Reduction ◽  
Stimulation Of

To test the hypothesis that stimulation of adrenergic receptors in the heart is maximal during maximal exercise, and to determine whether generalized stimulation of adrenergic receptors during strenuous exercise produces significant alterations in the normal regional distribution of blood flow that occurs during exercise, we evaluated the cardiovascular effects of the infusion of dobutamine (40 micrograms.kg-1.min-1) in mongrel dogs during treadmill running. During maximal exercise, the dobutamine infusion resulted in a significant (P less than 0.05) increase in heart rate. Exercise capacity, total body O2 consumption (VO2), and maximal arteriovenous O2 difference, however, each were reduced during the infusion of this drug. A concomitant reduction in maximal blood flow to locomotive skeletal muscle occurred. The infusion of dobutamine also resulted in an increase in heart rate at a strenuous level of submaximal exercise. However, unlike during maximal exercise, VO2 was unchanged. Blood flow to locomotive skeletal muscle increased, and there was a concomitant reduction in arteriovenous O2 difference. Blood flow reductions that normally occur in splanchnic circulations during strenuous and during maximal exercise were generally somewhat attenuated during the infusion of this drug. Thus, dobutamine, a sympathomimetic agent, produces significant cardiovascular effects when infused in high doses during exercise. Our results demonstrate that beta-adrenergic receptor reserve exists in the heart during maximal exercise in dogs. In addition, the peripheral responses that occur during the infusion of the drug provide additional evidence that different degrees of adrenergic receptor reserve normally appear to be present within different regional circulations during strenuous and during maximal exercise.

Genetic Polymorphisms in the Promoter Region of the beta-2 Adrenergic Receptor Are Associated with the Early Response of Acute Lymphoblastic Leukemia to Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1959-1959
Author(s):  
Meyling H. Cheok ◽  
Cong Ding ◽  
Wenjian Yang ◽  
Somas Das ◽  
Dario Campana ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Adrenergic Receptor ◽  
Lymphoblastic Leukemia ◽  
Receptor Gene ◽  
High Dose ◽  
A Genome ◽  
Adrb2 Gene ◽  
Beta 2

Abstract Acute lymphoblastic leukemia (ALL) in children is a paradigm of disseminated cancer that is curable with chemotherapy, yet current treatment fails to cure about 20% of patients, for reasons that remain unknown. In a genome-wide assessment of in vivo treatment-induced changes in gene expression in ALL cells using the Affymetrix U95A and U133A oligonucleotide microarray, we found that patients who eventually relapsed did not up-regulate expression of the pro-apoptotic beta-2 adrenergic receptor gene (ADRB2) in their ALL cells after initial treatment with methotrexate and mercaptopurine. After treatment we observed a 5-fold lower level of ADRB2 gene expression in leukemia cells of patients who ultimately relapsed. We found a common genetic polymorphism in the ADRB2 promoter that was significantly linked to high-dose methotrexate induced up-regulation in ADRB2 gene expression in ALL cells. Moreover, the ADRB2 promoter haplotype was significantly linked to poor early treatment response in ALL cells from 242 children (i.e., probability of event-free survival at two years, p=0.0275 stratified by risk groups). These findings have revealed a germline polymorphism that is linked to the early antileukemic effects of ALL chemotherapy and provide new insights into genetic determinants of ALL treatment efficacy.

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