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L Toll

Publications and source records attributed to L Toll.

60 records · Page 4Linked to original sources
PubMed1982

Solubilization and Characterization of Histamine H1 receptors in brain.

[3H]Doxepin, a tricyclic antidepressant, binds with high affinity to guinea pig brain membranes with a drug specificity indicating an association with H1 histamine receptors. The [3H]doxepin binding site has been solubilized, with digitonin being the only detergent able to maintain specific binding after solubilization. After solubilization, the kinetics and drug specificity of binding are virtually identical with those obtained in the intact membranes, indicating a conservation of the transmitter binding site after removal of the receptor from its lipid environment. The regulation of agonist affinity for the histamine H1 receptor by cations is maintained after solubilization. Sodium and to a similar extent lithium, but not potassium, rubidium, or cesium, decrease the affinity of agonists for the receptor. The divalent cations manganese and magnesium maintain their ability to increase agonist affinity after solubilization. Guanine nucleotides, however, lose their ability to decrease agonist affinity for the histamine H1 receptor after solubilization. Histamine receptors in rat brain differ from guinea pig brain receptors in the potency of several antihistamines. The difference is maintained in the solubilized receptors. Sucrose gradient and gel filtration experiments indicated Mr approximately 430,000 for the receptor-digitonin complex. The isoelectric point of the receptor is 4.8. None of these physical techniques distinguishes between guinea pig and rat brain receptors.

Animals↗
PubMed1981

[3H]doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates.

[3H]Doxepin, a tricyclic antidepressant, binds to brain homogenates with two saturable components. The high affinity component, with a dissociation constant (KD) of 0.26 nM, is associated with histamine H1-receptors. This high affinity binding shows stereospecificity in that d-chlorpheniramine is 100 times more potent than the pharmacologically less active l-isomer. Its drug specificity and regional variation closely parallel those exhibited by [3H]mepyramine binding. The drug specificity of the low affinity component is distinct from that of histamine H1-receptors, with no stereospecificity for chlorpheniramine isomers. Furthermore, all the H1-histamine antagonists tested display micromolar potency at the low-affinity doxepin sites but nanomolar potency at the high-affinity doxepin sites associated with a physiological histamine H1-receptor. The drug specificity of the low affinity site does not correspond to that of any known neurotransmitter receptor. Tricyclic antidepressants display IC50 values of 30-600 nM for the inhibition of [3H]doxepin binding to the low-affinity component with most values in the 0.1-0.3 microM affinity range.

Animals↗
PubMed1980

Evidence that an ATPase and a protonmotive force function in the transport of acetylcholine into storage vesicles.

PC12, a clonal line of rat pheochromocytoma, accumulates newly synthesized acetylcholine in storage granules. The accumulation of acetylcholine in PC12 granules, but not acetylcholine synthesis, was inhibited by treatment of the cells with any of several inhibitors of energy metabolism. These included nigericin, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, dicyclohexylcarbodiimide, and iodoacetate. Valinomycin alone and oligomycin were without effect. Except for iodoacetate, these agents did not exert their effects on acetylcholine storage by depleting the cells of ATP.

Acetylcholine↗
PubMed1977

Energy utilization in the uptake of catecholamines by synaptic vesicles and adrenal chromaffin granules.

Several inhibitors of energy metabolism decreased the ATP-stimulated uptake of catecholamines by isolated synaptic vesicles from rat brain and by chromaffin granules from bovine adrenal medulla. Catecholamine uptake was inhibited by dinitrophenol, S-13 and oleic acid, which are known to block active transport by dissipating trans-membrane proton gradients. Thus a proton gradient appears to be involved in catecholamine transport. Both catecholamine uptake and vesicle-associated Ca2+/Mg2+-ATPase were inhibited by dicyclohexylcarbodiimide and tributyltin, which had previously been shown to inhibit the Ca2+/Mg2+-ATPase of mitochondria. However, mitochondrial ATPase was not involved in catecholamine uptake as oligomycin and aurovertin, more specific inhibitors of mitochondrial ATPase, did not affect catecholamine uptake. It is suggested that ATP stimulates catecholamine uptake by serving as a substrate for the ATPase. Activity of this enzyme causes translocation of protons across the vesicle membrane establishing a trans-membrane proton gradient. The proton gradient drives the transport of catecholamines.

Adenosine Triphosphate↗