Receptor Number (receptor + number)

Distribution by Scientific Domains


Selected Abstracts


Chronic Ethanol Administration Alters Immunoreactivity for GABAA Receptor Subunits in Rat Cortex in a Region-Specific Manner

ALCOHOLISM, Issue 8 2000
A. Chistina Grobin
Background: Chronic ethanol administration has a plethora of physiological effects. Among the most consistently observed findings is a change in the expression pattern of ,-aminobutyric acid type A (GABAA) receptor subunits in the rat brain cortex. These findings led to the hypothesis of "subunit substitution" to account for changes in receptor function without changes in receptor number. Methods: We used subunit (,1 and ,4) specific antibodies and a combination of immunohistochemistry and immunoblotting to examine subregions of cortex (prefrontal, cingulate, motor, parietal, and piriform) for their response to 2 weeks of forced ethanol administration. Results: Overall, cortical immunoreactivity for the ,1 subunit was decreased and for the ,4 subunit increased whether measured immunohistochemically or by immunoblotting. Piriform cortex exhibited a bidirectional change in GABAA receptor ,1 and ,4 immunoreactivity, similar to that previously observed in preparations of whole cortex. However, in parietal cortex, declines in ,1 immunoreactivity (55 ± 12% control value [CV] and 88.3 ± 4.3% CV; immunohistochemistry and immunoblotting, respectively) were not accompanied by concomitant increases in ,4 immunoreactivity (104 ± 8% CV and 116 ± 9.3% CV; immunohistochemistry and immunoblotting, respectively). Conversely, ,4 immunoreactivity increased in cingulate cortex (210 ± 30% CV and 134 ± 9.5% CV; immunohistochemistry and immunoblotting, respectively) without a decline in ,1 immunoreactivity (90 ± 4% CV and 91.3 ± 3.9% CV; immunohistochemistry and immunoblotting, respectively). Prefrontal and motor cortex exhibited GABAA receptor subunit peptide alterations, but these changes varied with the method of analysis. Conclusions: These findings demonstrate that ethanol dependence results in nonuniform changes in GABAA receptor subunit peptide levels across the rat brain cortex and suggest that mechanisms which subserve functional changes in receptor activity may vary in accordance with anatomic or cellular differences within the cortex. [source]


Sex differences in response to steroids in preterm sheep lungs are not explained by glucocorticoid receptor number or binding affinity,

PEDIATRIC PULMONOLOGY, Issue 1 2001
Jana Kovar BScHons
Abstract We recently reported that prenatal glucocorticoid therapy is less effective at promoting an improvement in lung function in male than in female sheep. This observation, and the higher incidence of respiratory distress syndrome in human males, suggests that the male fetal lung may be less responsive to glucocorticoids than is the female fetal lung. Since glucocorticoids are known to exert their effects via specific cytoplasmic glucocorticoid receptors (GR), we hypothesized that there may be sexual dimorphism in either the number or binding affinity of lung GR. To test the hypothesis, binding of dexamethasone (a synthetic glucocorticoid, 0.5,40 nM) by cytosolic fractions of male (n,=,16) and female (n,=,16) fetal sheep lung was measured at 125 days gestation (term,=,148 days). Scatchard analysis of dexamethasone binding showed that the total number of GR (Bmax) did not significantly differ between male (346,±,42 fmol/mg protein) and female (277,±,23 fmol/mg protein) fetuses. The measured binding affinity (Kd) in male fetal lungs (6.85,±,0.43 nM) was not significantly different from that in females (8.46,±,1.02 nM). In conclusion, this study suggests that sex differences in fetal sheep lung responses to glucocorticoid therapy are not due to differences in the number or binding affinity of lung GR. Pediatr Pulmonol. 2001; 32:8,13. © 2001 Wiley-Liss, Inc. [source]


Evidence of dysfunctional ,2 -adrenoceptor signal system in pre-eclampsia

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 1 2000
B. Aune Senior Registrar
Objectives To determine how ,2 -adrenoceptor binding and function differ between healthy women and those with pre-eclampsia. Design Case-control study. Setting Faculty of Medicine, University of Tromsų, Norway. Participants Two groups of pregnant women: eight cases with pre-eclampsia, matched with eight healthy controls. Methods Venous blood was drawn from women in both groups after an overnight rest. The two groups were matched for gestational age which was (mean (SD)) 36.4 (3.8) and 36.5 (4.4) weeks for the pre-eclamptic and control groups, respectively. Six weeks after delivery a second blood sample was obtained. The binding and function of ,2 -adrenoceptors were determined in isolated human mononu-clear leukocytes. The levels of adrenaline and noradrenaline were determined in plasma from venous blood. Results An elevated density of functional ,2 -adrenoceptors was observed in normal pregnancy [mean (SD) 390 (90) vs 270 (60) sites/cell postpartum], due to an increased fraction of receptors in high affinity state, with unaltered total receptor density. The number of functional ,2 -adrenoceptors was reduced in pre-eclampsia [mean (SD) 80 (40) vs 240 (30) sites/cell postpartum], due to a reduction in the total receptor number with an unaltered fraction of high affinity receptors. In pregnancy, both unstimulated and isoprenaline-stimulated cAMP levels were reduced in the women with pre-eclampsia (0.5 (0.2) and 1.7 (0.9) pmol/106 cells, respectively) compared with the normal pregnant controls (mean (SD) 1.2 (0.3) and 4.7 (1.8) pmol/106 cells, respectively). Plasma catecholamine levels were not elevated in the women with pre-eclampsia. Conclusions The increased number of functional ,2 -adrenoceptors may contribute to the vasodilatation seen in normal pregnancy, while the reduced overall number of receptors may be one of several factors that account for increased peripheral vascular resistance in pre-eclampsia. [source]


Characterisation of ligand binding to the parathyroid hormone/parathyroid hormone-related peptide receptor in MCF7 breast cancer cells and SaOS-2 osteosarcoma cells

CELL BIOCHEMISTRY AND FUNCTION, Issue 2 2007
Majed S. Alokail
Abstract Parathyroid hormone-related peptide (PTHrP) and parathyroid hormone (PTH)/PTHrP-receptor, PTH/PTHrP-R, are frequently expressed in mammary carcinomas as well as in bone cells. In this study we compared the ligand binding characteristics of the PTH/PTHrP,R in SaOS-2 human osteosarcoma cells with those in MCF7 breast cancer cells. We used both Scatchard analysis of saturation kinetics for iodinated ligand and the level of expressed receptor protein by visualising the single radio-labelled receptor-ligand complex from isolated membrane preparations from the two cell lines. In MCF7 cells, ligand binding, (receptor number) was increased by prior exposure of the cultured cells to epidermal growth factor (EGF), estradiol (E2), or dexamethasone (DEX), and decreased following calcitriol (1,25 DHCC). In contrast in the SaOS-2 cells, PTH/PTHrP-R number was increased by exposure to E2 and 1,25DHCC and decreased by DEX while EGF had no effect. These data were confirmed when the PTH/PTHrP-R was cross linked with 125I-PTHrP-1-34Tyr, and extended by visualising the intensity of the isolated radiolabelled receptor complex by autoradiography following SDS-PAGE at several time points during the treatment. Copyright © 2005 John Wiley & Sons, Ltd. [source]


Nicotinic ,5 subunit deletion locally reduces high-affinity agonist activation without altering nicotinic receptor numbers

JOURNAL OF NEUROCHEMISTRY, Issue 1 2007
Robert W. B. Brown
Abstract Neuronal nicotinic acetylcholine receptor subunit ,5 mRNA is widely expressed in the CNS. An ,5 gene polymorphism has been implicated in behavioral differences between mouse strains, and ,5-null mutation induces profound changes in mouse acute responses to nicotine. In this study, we have examined the distribution and prevalence of ,5* nicotinic acetylcholine receptor in mouse brain, and quantified the effects of ,5-null mutation on pre-synaptic nicotinic acetylcholine receptor function (measured using synaptosomal 86Rb+ efflux) and overall [125I]epibatidine binding site expression. ,5* nicotinic acetylcholine receptor expression was found in nine of fifteen regions examined, although < 20% of the total nicotinic acetylcholine receptor population in any region contained ,5. Deletion of the ,5 subunit gene resulted in localized loss of function (thalamus, striatum), which was itself confined to the DH,E-sensitive receptor population. No changes in receptor expression were seen. Consequently, functional changes must occur as a result of altered function per unit of receptor. The selective depletion of high agonist activation affinity sites results in overall nicotinic function being reduced, and increases the overall agonist activation affinity. Together, these results describe the receptor-level changes underlying altered behavioral responses to nicotine in nicotinic acetylcholine receptor ,5 subunit-null mutants. [source]