The Experts below are selected from a list of 5322 Experts worldwide ranked by ideXlab platform
Gary Rudnick - One of the best experts on this subject based on the ideXlab platform.
-
amphetAmine derivatives interact with both plasma membrane and secretory vesicle biogenic Amine Transporters
Molecular Pharmacology, 1993Co-Authors: S Schuldiner, Sonia Steinermordoch, Rodrigo Yelin, Stephen C Wall, Gary RudnickAbstract:The interaction of fenflurAmine, 3,4-methylenedioxymethamphetAmine (MDMA), and p-chloroamphetAmine (PCA) with the platelet plasma membrane serotonin Transporter and the vesicular Amine Transporter were studied using both Transport and binding measurements. FenflurAmine is apparently a substrate for the plasma membrane Transporter, and consequently inhibits both serotonin Transport and imiprAmine binding. Moreover, fenflurAmine exchanges with internal [3H]serotonin in a plasma membrane Transporter-mediated reaction that requires NaCl and is blocked by imiprAmine. These properties are similar to those of MDMA and PCA as previously described. In adrenal chromaffin granule membrane vesicles containing the vesicular Amine Transporter, fenflurAmine inhibited serotonin Transport and dissipated the transmembrane pH difference (delta pH) that drives Amine uptake. The use of [3H]reserpine-binding measurements to determine drug interaction with the vesicular Amine Transporter allowed assessment of the relative ability of MDMA, PCA, and fenflurAmine to bind to the substrate site of the vesicular Transporter. These measurements permit a distinction between inhibition of vesicular serotonin Transport by directly blocking vesicular Amine Transport and by dissipating delta pH. The results indicate that MDMA and fenflurAmine inhibit by both mechanisms but PCA dissipates delta pH without blocking vesicular Amine Transport directly.
-
from synapse to vesicle the reuptake and storage of biogenic Amine neurotransmitters
Biochimica et Biophysica Acta, 1993Co-Authors: Gary Rudnick, Janet A ClarkAbstract:Department of Pharmacology, Yale University School of Medicine, New Haven, CT (USA) (Received 2 June 1993) Key words: Neurotransmitter; Neurotransmitter Transport; Transport regulation; Biogenic Amine; eDNA Contents I. Overview 249 II. What do the Transporters do? 250 III. How do they do it? 250 A. Ionic requirements 251 B. Stoichiometry 252 C. Mechanism 253 IV. Identification and characterization of Na+-dependent biogenic Amine Transporter eDNA ...... 255 V. How is Na+-dependent biogenic Amine Transport regulated? 258 VI. How do storage vesicles Transport Amines? 260 VII. Cloning the vesicular Amine Transporter cDNA 261 VIII. Summary 261 References 261 I. Overview The Na +- and Cl--coupled neurotransmitter trans- porters represent a fascinating group of integral mem- brane proteins encoded by a closely related family of recently cloned cDNAs [1-20]. These carrier proteins couple the transmembrane movement of Na +, CI- and in some systems K +, to the reuptake of neurotrans- Correspondence to: G. Rudnick, Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. mitters released into the synaptic cleft [21] (Fig. 1). As such, they function to regulate neurotransmitter activ- ity by removing extracellular transmitter. Inhibitors that interfere with this regulation include antidepres- sant drugs and stimulants, such as the amphetAmines and cocaine. Of the plasma membrane Transporters which have been studied, three proteins responsible for catalyzing Transport of serotonin (5-hydroxytryptAmine (5-HT) [3,4] and the catecholAmines norepinephrine (NE) [2] and dopAmine (DA) [5-7,17]) stand out as a distinct subfamily. These biogenic Amine Transporters are all inhibited by cocaine, and share other structural and mechanistic properties.
-
from synapse to vesicle the reuptake and storage of biogenic Amine neurotransmitters
Biochimica et Biophysica Acta, 1993Co-Authors: Gary Rudnick, Janet A ClarkAbstract:Department of Pharmacology, Yale University School of Medicine, New Haven, CT (USA) (Received 2 June 1993) Key words: Neurotransmitter; Neurotransmitter Transport; Transport regulation; Biogenic Amine; eDNA Contents I. Overview 249 II. What do the Transporters do? 250 III. How do they do it? 250 A. Ionic requirements 251 B. Stoichiometry 252 C. Mechanism 253 IV. Identification and characterization of Na+-dependent biogenic Amine Transporter eDNA ...... 255 V. How is Na+-dependent biogenic Amine Transport regulated? 258 VI. How do storage vesicles Transport Amines? 260 VII. Cloning the vesicular Amine Transporter cDNA 261 VIII. Summary 261 References 261 I. Overview The Na +- and Cl--coupled neurotransmitter trans- porters represent a fascinating group of integral mem- brane proteins encoded by a closely related family of recently cloned cDNAs [1-20]. These carrier proteins couple the transmembrane movement of Na +, CI- and in some systems K +, to the reuptake of neurotrans- Correspondence to: G. Rudnick, Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. mitters released into the synaptic cleft [21] (Fig. 1). As such, they function to regulate neurotransmitter activ- ity by removing extracellular transmitter. Inhibitors that interfere with this regulation include antidepres- sant drugs and stimulants, such as the amphetAmines and cocaine. Of the plasma membrane Transporters which have been studied, three proteins responsible for catalyzing Transport of serotonin (5-hydroxytryptAmine (5-HT) [3,4] and the catecholAmines norepinephrine (NE) [2] and dopAmine (DA) [5-7,17]) stand out as a distinct subfamily. These biogenic Amine Transporters are all inhibited by cocaine, and share other structural and mechanistic properties.
Janet A Clark - One of the best experts on this subject based on the ideXlab platform.
-
from synapse to vesicle the reuptake and storage of biogenic Amine neurotransmitters
Biochimica et Biophysica Acta, 1993Co-Authors: Gary Rudnick, Janet A ClarkAbstract:Department of Pharmacology, Yale University School of Medicine, New Haven, CT (USA) (Received 2 June 1993) Key words: Neurotransmitter; Neurotransmitter Transport; Transport regulation; Biogenic Amine; eDNA Contents I. Overview 249 II. What do the Transporters do? 250 III. How do they do it? 250 A. Ionic requirements 251 B. Stoichiometry 252 C. Mechanism 253 IV. Identification and characterization of Na+-dependent biogenic Amine Transporter eDNA ...... 255 V. How is Na+-dependent biogenic Amine Transport regulated? 258 VI. How do storage vesicles Transport Amines? 260 VII. Cloning the vesicular Amine Transporter cDNA 261 VIII. Summary 261 References 261 I. Overview The Na +- and Cl--coupled neurotransmitter trans- porters represent a fascinating group of integral mem- brane proteins encoded by a closely related family of recently cloned cDNAs [1-20]. These carrier proteins couple the transmembrane movement of Na +, CI- and in some systems K +, to the reuptake of neurotrans- Correspondence to: G. Rudnick, Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. mitters released into the synaptic cleft [21] (Fig. 1). As such, they function to regulate neurotransmitter activ- ity by removing extracellular transmitter. Inhibitors that interfere with this regulation include antidepres- sant drugs and stimulants, such as the amphetAmines and cocaine. Of the plasma membrane Transporters which have been studied, three proteins responsible for catalyzing Transport of serotonin (5-hydroxytryptAmine (5-HT) [3,4] and the catecholAmines norepinephrine (NE) [2] and dopAmine (DA) [5-7,17]) stand out as a distinct subfamily. These biogenic Amine Transporters are all inhibited by cocaine, and share other structural and mechanistic properties.
-
from synapse to vesicle the reuptake and storage of biogenic Amine neurotransmitters
Biochimica et Biophysica Acta, 1993Co-Authors: Gary Rudnick, Janet A ClarkAbstract:Department of Pharmacology, Yale University School of Medicine, New Haven, CT (USA) (Received 2 June 1993) Key words: Neurotransmitter; Neurotransmitter Transport; Transport regulation; Biogenic Amine; eDNA Contents I. Overview 249 II. What do the Transporters do? 250 III. How do they do it? 250 A. Ionic requirements 251 B. Stoichiometry 252 C. Mechanism 253 IV. Identification and characterization of Na+-dependent biogenic Amine Transporter eDNA ...... 255 V. How is Na+-dependent biogenic Amine Transport regulated? 258 VI. How do storage vesicles Transport Amines? 260 VII. Cloning the vesicular Amine Transporter cDNA 261 VIII. Summary 261 References 261 I. Overview The Na +- and Cl--coupled neurotransmitter trans- porters represent a fascinating group of integral mem- brane proteins encoded by a closely related family of recently cloned cDNAs [1-20]. These carrier proteins couple the transmembrane movement of Na +, CI- and in some systems K +, to the reuptake of neurotrans- Correspondence to: G. Rudnick, Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. mitters released into the synaptic cleft [21] (Fig. 1). As such, they function to regulate neurotransmitter activ- ity by removing extracellular transmitter. Inhibitors that interfere with this regulation include antidepres- sant drugs and stimulants, such as the amphetAmines and cocaine. Of the plasma membrane Transporters which have been studied, three proteins responsible for catalyzing Transport of serotonin (5-hydroxytryptAmine (5-HT) [3,4] and the catecholAmines norepinephrine (NE) [2] and dopAmine (DA) [5-7,17]) stand out as a distinct subfamily. These biogenic Amine Transporters are all inhibited by cocaine, and share other structural and mechanistic properties.
Robert H Edwards - One of the best experts on this subject based on the ideXlab platform.
-
the chromaffin granule and synaptic vesicle Amine Transporters differ in substrate recognition and sensitivity to inhibitors
Journal of Biological Chemistry, 1994Co-Authors: Doris Peter, J. Jimenez, Robert H EdwardsAbstract:Abstract Classical studies using bovine chromaffin granules have defined the physiologic and pharmacologic properties of the vesicular Amine Transporter that packages monoAmine transmitters into intracellular vesicles for subsequent regulated release. The recent isolation of two distinct but closely related cDNA clones encoding vesicular Amine Transport suggests that the activity expressed in the brain (synaptic vesicle Amine Transporter or SVAT) may differ significantly from the previously described adrenal gland activity (chromaffin granule Amine Transporter or CGAT). A direct comparison of the two Transporters now shows that SVAT has a higher affinity than CGAT for monoAmine substrates, in particular for histAmine. In addition, SVAT shows approximately 10-fold greater sensitivity to tetrabenazine than CGAT. [3H]Dihydrotetrabenazine shows no detectable binding to CGAT but does bind to SVAT, accounting for the differential sensitivity. Furthermore, methamphetAmine preferentially inhibits Transport by SVAT relative to CGAT, apparently by competing at the site of Amine recognition rather than by disrupting the vesicular pH gradient. These previously unsuspected differences in the storage of monoAmine transmitter in the central nervous system and the adrenal gland may help to account for several classic pharmacological observations.
-
reserpine binding to a vesicular Amine Transporter expressed in chinese hamster ovary fibroblasts
Journal of Biological Chemistry, 1993Co-Authors: S Schuldiner, Yongjian Liu, Robert H EdwardsAbstract:The potent antihypertensive drug reserpine inhibits the Transport of biogenic Amines into adrenal chromaffin granules and synaptic vesicles. Reserpine acts by binding almost irreversibly to the vesicular Amine Transporter, and this interaction has been used both to study the mechanism of Transport and to purify the protein responsible. Recent isolation of a cDNA for the rat chromaffin granule Amine Transporter (CGAT) by selection in the neurotoxin 1-methyl-4-phenylpyridinium now permits an analysis of the interaction with reserpine at a molecular level. Using membranes from stable transformants expressing the Transporter, we show that reserpine binds specifically and quantitatively to CGAT. As with the native protein in bovine chromaffin granules, a pH gradient accelerates reserpine binding, and Amine substrates compete for binding with reserpine. However, 1-methyl-4-phenylpyridinium and tetrabenazine, the other principal inhibitor of vesicular Amine Transport, compete very poorly with reserpine for binding, suggesting that they interact with CGAT at distinct sites.
S Schuldiner - One of the best experts on this subject based on the ideXlab platform.
-
amphetAmine derivatives interact with both plasma membrane and secretory vesicle biogenic Amine Transporters
Molecular Pharmacology, 1993Co-Authors: S Schuldiner, Sonia Steinermordoch, Rodrigo Yelin, Stephen C Wall, Gary RudnickAbstract:The interaction of fenflurAmine, 3,4-methylenedioxymethamphetAmine (MDMA), and p-chloroamphetAmine (PCA) with the platelet plasma membrane serotonin Transporter and the vesicular Amine Transporter were studied using both Transport and binding measurements. FenflurAmine is apparently a substrate for the plasma membrane Transporter, and consequently inhibits both serotonin Transport and imiprAmine binding. Moreover, fenflurAmine exchanges with internal [3H]serotonin in a plasma membrane Transporter-mediated reaction that requires NaCl and is blocked by imiprAmine. These properties are similar to those of MDMA and PCA as previously described. In adrenal chromaffin granule membrane vesicles containing the vesicular Amine Transporter, fenflurAmine inhibited serotonin Transport and dissipated the transmembrane pH difference (delta pH) that drives Amine uptake. The use of [3H]reserpine-binding measurements to determine drug interaction with the vesicular Amine Transporter allowed assessment of the relative ability of MDMA, PCA, and fenflurAmine to bind to the substrate site of the vesicular Transporter. These measurements permit a distinction between inhibition of vesicular serotonin Transport by directly blocking vesicular Amine Transport and by dissipating delta pH. The results indicate that MDMA and fenflurAmine inhibit by both mechanisms but PCA dissipates delta pH without blocking vesicular Amine Transport directly.
-
reserpine binding to a vesicular Amine Transporter expressed in chinese hamster ovary fibroblasts
Journal of Biological Chemistry, 1993Co-Authors: S Schuldiner, Yongjian Liu, Robert H EdwardsAbstract:The potent antihypertensive drug reserpine inhibits the Transport of biogenic Amines into adrenal chromaffin granules and synaptic vesicles. Reserpine acts by binding almost irreversibly to the vesicular Amine Transporter, and this interaction has been used both to study the mechanism of Transport and to purify the protein responsible. Recent isolation of a cDNA for the rat chromaffin granule Amine Transporter (CGAT) by selection in the neurotoxin 1-methyl-4-phenylpyridinium now permits an analysis of the interaction with reserpine at a molecular level. Using membranes from stable transformants expressing the Transporter, we show that reserpine binds specifically and quantitatively to CGAT. As with the native protein in bovine chromaffin granules, a pH gradient accelerates reserpine binding, and Amine substrates compete for binding with reserpine. However, 1-methyl-4-phenylpyridinium and tetrabenazine, the other principal inhibitor of vesicular Amine Transport, compete very poorly with reserpine for binding, suggesting that they interact with CGAT at distinct sites.
A Scarpa - One of the best experts on this subject based on the ideXlab platform.
-
Amine Transport into chromaffin ghosts kinetic measurements of net uptake of biologically and pharmacologically relevant Amines using an on line amperometric technique
FEBS Journal, 2008Co-Authors: Sally E Carty, Robert G Johnson, Tom Vaughan, Adam Pallant, A ScarpaAbstract:The kinetic parameters for net Transport of dopAmine, epinephrine, norepinephrine, 5-hydroxytryptAmine, S alpha-methyldopAmine, R alpha-methyldopAmine, and 1R,2S alpha-methylnorepinephrine into highly purified bovine chromaffin ghosts were determined using an on-line amperometric technique. Chromaffin ghosts devoid of endogenous Amines were formed from lysis of chromaffin granules under hypotonic conditions, extensive washing of the scattered membranes, followed by resuspension in iso-osmotic media and overnight dialysis. When chromaffin ghosts formed so as to generate and maintain a large delta pH were suspended in 185 mM KCl, 10 mM Hepes at pH 7.0, 37 degrees C, the addition of MgATP resulted in rapid acidification of the intravesicular space, which was maintained at pH 6.0 (+/- 0.1) for over 30 min. Kinetic net Amine Transport was subsequently measured with a glassy carbon electrode. The initial rates of uptake were found to follow Michaelis-Menten kinetics. Computer based statistical analysis of the data using distribution-free procedures yielded Km (and V) values as follows: in microM (nmol X mg protein-1 X min-1) dopAmine, 16.2 (14.0); R-norepinephrine, 32.5 (12.9); R-epinephrine, 35.1 (15.2); 5-hydroxytryptAmine, 4.7 (5.1); S alpha-methyldopAmine, 17.7 (11.2); R alpha-methyldopAmine, 44.2 (9.9); 1R,2S alpha-methylnorepinephrine, 76.5 (12.5). The physiologic and pharmacologic implications of these kinetic parameters are discussed.