The Experts below are selected from a list of 66 Experts worldwide ranked by ideXlab platform
C R Dermon - One of the best experts on this subject based on the ideXlab platform.
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comparative anatomy of α2 and β adrenoceptors in the adult and developing brain of the marine teleost the red porgy pagrus pagrus sparidae 3h clonidine and 3h Dihydroalprenolol quantitative autoradiography and receptor subtypes immunohistochemistry
The Journal of Comparative Neurology, 2005Co-Authors: Basileios Zikopoulos, C R DermonAbstract:The present study aimed to determine the anatomic distribution and developmental profile of alpha(2) and beta adrenoceptors (AR) in marine teleost brain. Alpha 2 and beta adrenoceptors were studied at different developmental stages by using [(3)H]clonidine and [(3)H]Dihydroalprenolol, respectively, by means of in vitro quantitative autoradiography. Furthermore, immunohistochemical localization of the receptor subtypes was performed to determine their cellular distribution. Saturation studies determined a high-affinity component of [(3)H]clonidine and [(3)H]Dihydroalprenolol binding sites. High levels of both receptors were found in preglomerular complex, ventral hypothalamus, and lateral torus. Dorsal hypothalamus and isthmus included high levels of alpha(2) AR, whereas pretectum and molecular and proliferative zone of cerebellum were specifically characterized by high densities of beta AR. From the first year of life, adult levels of both AR were found in most medial telencephalic, hypothalamic, and posterior tegmental areas. Decreases in both receptors densities with age were prominent in ventral and posterior telencephalic, pretectal, ventral thalamic, hypothalamic, and tegmental brain regions. Immunohistochemical data were well correlated with autoradiography and demonstrated the presence of alpha(2A), alpha(2C), beta(1), and beta(2) AR subtype-like immunoreactivity. Both the neuronal (perikaryal or dendritic) and the glial localization of receptors was revealed. The localization and age-dependent alterations in alpha(2) and beta AR were parallel to plasticity mechanisms, such as cell proliferation in periventricular thalamus, hypothalamus, and cerebellum. In addition, the biochemical characteristics, distribution pattern, and neuronal or glial specificity of the receptors in teleost brain support a similar profile of noradrenergic transmission in vertebrate brain evolution.
Graeme Milligan - One of the best experts on this subject based on the ideXlab platform.
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up regulation of a constitutively active form of the β2 adrenoceptor by sustained treatment with inverse agonists but not antagonists
FEBS Letters, 1996Co-Authors: David J Macewan, Graeme MilliganAbstract:In neuroblastoma X glioma hybrid, NG1O8-15, cells transfected to stably express a constitutively active mutant (CAM) form of the human beta2-adrenoceptor, the beta-adrenoceptor ligands sotalol and betaxolol functioned as inverse agonists as they reduced basal adenylyl cyclase activity whereas the antagonists Dihydroalprenolol and propranolol did not. Maintained presence of the CAMbeta2-adrenoceptor inverse agonists but not the antagonists in the culture medium of the cells resulted in a substantial, concentration-dependent, up-regulation of the CAMbeta2-adrenoceptor. Up-regulation of the CAMbeta2-adrenoceptor by the inverse agonists was prevented by co-incubation of the cells with either propranolol or Dihydroalprenolol. Neither maintained elevation of cAMP levels nor the inhibition of adenylyl cyclase activity altered the ability of the inverse agonist ligands to cause receptor up-regulation.
Daniel D Savage - One of the best experts on this subject based on the ideXlab platform.
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alterations in spleen norepinephrine and lymphocyte 3h Dihydroalprenolol binding site number in genetically epilepsy prone rats
Brain Behavior and Immunity, 1993Co-Authors: James A Carr, K A Ortiz, L L Paxton, L C Saland, Daniel D SavageAbstract:Abstract Noradrenergic neurotransmission plays an important role in normal immune reactivity. Genetically epilepsy-prone (GEPR-9) rats exhibit deficits in central noradrenergic systems and diminished plaque-forming cell responses following immunization in vivo . In the present study we examined the hypothesis that immunosuppression in GEPR-9 rats is associated with alterations in the splenic noradrenergic system. The content of norepinephrine (NE) in spleens of GEPR-9 age-matched nonepileptic Sprague–Dawley control rats was determined by high-performance liquid chromatography coupled with electrochemical detection (HPLC–EC). In addition, we measured the number of β-adrenergic receptors on splenic lymphocyte membranes of GEPR-9 and control rats using the β-adrenergic receptor antagonist Dihydroalprenolol ([ 3 H]DHA). HPLC–EC analysis revealed that splenic norepinephrine content was significantly greater in GEPR-9 rats than in controls. Results from receptor binding studies indicated a 33% reduction in specific binding of [ 3 H]DHA to splenic lymphocyte membranes of GEPR-9 rats. Saturation of binding studies revealed a significant decrease in the maximum number of [ 3 H]DHA binding sites on splenic lymphocyte membranes from GEPR-9 rats. These results indicate that the noradrenergic system in GEPR-9 rat spleen is altered. Whether either or both of these changes contribute to reduced immune reactivity in GEPR-9 rats remains to be determined.
Basileios Zikopoulos - One of the best experts on this subject based on the ideXlab platform.
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comparative anatomy of α2 and β adrenoceptors in the adult and developing brain of the marine teleost the red porgy pagrus pagrus sparidae 3h clonidine and 3h Dihydroalprenolol quantitative autoradiography and receptor subtypes immunohistochemistry
The Journal of Comparative Neurology, 2005Co-Authors: Basileios Zikopoulos, C R DermonAbstract:The present study aimed to determine the anatomic distribution and developmental profile of alpha(2) and beta adrenoceptors (AR) in marine teleost brain. Alpha 2 and beta adrenoceptors were studied at different developmental stages by using [(3)H]clonidine and [(3)H]Dihydroalprenolol, respectively, by means of in vitro quantitative autoradiography. Furthermore, immunohistochemical localization of the receptor subtypes was performed to determine their cellular distribution. Saturation studies determined a high-affinity component of [(3)H]clonidine and [(3)H]Dihydroalprenolol binding sites. High levels of both receptors were found in preglomerular complex, ventral hypothalamus, and lateral torus. Dorsal hypothalamus and isthmus included high levels of alpha(2) AR, whereas pretectum and molecular and proliferative zone of cerebellum were specifically characterized by high densities of beta AR. From the first year of life, adult levels of both AR were found in most medial telencephalic, hypothalamic, and posterior tegmental areas. Decreases in both receptors densities with age were prominent in ventral and posterior telencephalic, pretectal, ventral thalamic, hypothalamic, and tegmental brain regions. Immunohistochemical data were well correlated with autoradiography and demonstrated the presence of alpha(2A), alpha(2C), beta(1), and beta(2) AR subtype-like immunoreactivity. Both the neuronal (perikaryal or dendritic) and the glial localization of receptors was revealed. The localization and age-dependent alterations in alpha(2) and beta AR were parallel to plasticity mechanisms, such as cell proliferation in periventricular thalamus, hypothalamus, and cerebellum. In addition, the biochemical characteristics, distribution pattern, and neuronal or glial specificity of the receptors in teleost brain support a similar profile of noradrenergic transmission in vertebrate brain evolution.
Luciano Manara - One of the best experts on this subject based on the ideXlab platform.
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phenylethanolaminotetralines compete with 3h Dihydroalprenolol binding to rat colon membranes without evidencing atypical β adrenergic sites
Biochemical Pharmacology, 1992Co-Authors: Marco Landi, Alberto Bianchetti, Tiziano Croci, Luciano ManaraAbstract:Abstract [ 3 H]Dihydroalprenolol ([ 3 H]DHA) specific binding (determined by the difference in the presence and absence of 20 μM (−)isoprenaline) to rat colon membranes was saturable ( B max = 39.6 frnol / mg protein), of high affinity ( K d = 0.87nM) and stereospecific ( ic 50 330 and 3510 nM for (-)- and (+)isoprenaline, respectively); the Hill coefficient was close to one, indicating binding homogeneity. [ 3 H]DHA (0.6 nM) specific binding was potently inhibited ( K i range 1.9–3.3 nM) by the non-selective β-adrenoceptor antagonists pindolol, alprenolol and propranolol, but not by the non-adrenergic compounds 5-hydroxytryptamine, 8-hydroxydipropylaminotetraline, methysergide, dopamine and verapamil ( K i > 10,000 nM). The selective β 1 - and β 2 -adrenoceptor antagonists CGP 20,712A and ICI 118,551 resulted in biphasic competition binding curves, whose low and high affinity components were compatible with two populations of binding sites accounting for about 75 (β 2 ) and 25% (β 1 ) of total sites. The relative competing potencies of reference adrenergic agonists also suggested a prevalence of β 2 -adrenergic sites. The new agonists phenylethanolaminotetralines (PEATs), highly selective for the atypical β-adrenoceptors whose abundance in rat colon has been confirmed by comprehensive functional studies, had variable affinity for the [ 3 H]DHA-labelled sites depending on chirality, but with no substantial correlation with their pharmacological potency. Only 40% of [ 3 H]DHA binding, at a concentration about 10 times its K d for high affinity sites (β 1 and β 2 ), was prevented by saturating concentrations of isoprenaline. Under this condition, the representative PEAT, SR 58611A, highly potent and selective for atypical β-adrenoceptors in functional tests, and its pharmacologically inactive enantiomer, both inhibited the residual binding equipotently. In conclusion, [ 3 H]DHA binding did not detect atypical β-adrenoceptor sites in rat colon membranes, most probably because of its weaker affinity for them than for the coexisting β 1 and β 2 sites. PEAT stereoisomers proved essential for assessing both the stereospecificity and the functional significance of this atypical binding and to compare their affinity for [ 3 H]DHA-labelled sites and pharmacological potency.