GTP uptake into rat brain synaptic vesicles

• Published in: Brain research Vol. 1070; no. 1; pp. 71 - 76
• Main Authors: Santos, Tiago G., Souza, Diogo O., Tasca, Carla I.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 27.01.2006; Amsterdam Elsevier; New York, NY
• Subjects: Adenosine Triphosphate - pharmacology; Animals; ATP-dependent uptake; Biochemistry and metabolism; Biological and medical sciences; Biological Transport - drug effects; Brain - metabolism; Ca(2+) Mg(2+)-ATPase - antagonists & inhibitors; Central nervous system; Cold Temperature; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Glutamic Acid - pharmacology; GTP; Guanine nucleotide; Guanosine Diphosphate - metabolism; Guanosine Monophosphate - pharmacology; Guanosine Triphosphate - metabolism; Guanosine Triphosphate - pharmacology; Guanylyl Imidodiphosphate - pharmacokinetics; Macrolides - pharmacology; Male; Neurotransmitter storage; Rats; Rats, Wistar; Synaptic vesicle; Synaptic Vesicles - metabolism; Time Factors; Vertebrates: nervous system and sense organs; GDP; GTP; Neurotransmitters, modulators, transporters and receptors; Guanine nucleotide; Synaptic vesicle; GppNHp; ATP-dependent uptake; GMP; Neurotransmitter storage; Rat; Rodentia; Central nervous system; Uptake; Encephalon; Vertebrata; Mammalia; Guanine nucleotide GTP Synaptic vesicle ATP-dependent uptake Neurotransmitter storage; Animal; Neurotransmitter; ATP
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2005.10.099

Uptake of neurotransmitters into synaptic vesicles is driven by an electrochemical gradient generated by a vacuolar-type proton pump ATPase. This uptake implies a key role for synaptic vesicles in the regulation of neurotransmitter systems. Guanine nucleoside and nucleotides are involved in the inhibition of glutamate-induced cellular responses via an extracellular action and diverse trophic, proliferative, and modulatory effects of guanine nucleotides on neural cells have been shown. Here, we characterized the uptake of GTP into synaptic vesicles isolated from whole rat brain, by using a tritiated poorly-hydrolyzable GTP analog, 5′-guanylylimidodiphosphate ([ 3H]GppNHp). Uptake of GTP into synaptic vesicles is saturable, time- and temperature-dependent, and relies on a proton-eletrochemical gradient. However, [ 3H]GMP and [ 3H]GDP radioactive labeling in synaptic vesicles is not dependent on temperature and vesicular ATPase activity, which indicates that these nucleotides only bind to and are not taken up into synaptic vesicles. GTP is taken up by the same eletrochemical gradient-dependent transport system, as are neurotransmitters storage, which indicates that this guanine nucleotide may also function as a neurotransmitter.