The human immunodeficiency virus-1 protein Tat and its discrete fragments evoke selective release of acetylcholine from human and rat cerebrocortical terminals through species-specific mechanisms
| Autor: | Santina Bruzzone, Massimo Grilli, Paolo Cavazzani, Luca Raiteri, Maurizio Raiteri, Anna Maria Pittaluga, Marco Feligioni, Roberto Pattarini |
|---|---|
| Předmět: |
Adult
Male Presynaptic Terminals Receptors Cytoplasmic and Nuclear Inositol 1 4 5-Trisphosphate Biology Tritium Choline Rats Sprague-Dawley chemistry.chemical_compound Species Specificity medicine Excitatory Amino Acid Agonists Animals Humans Inositol 1 4 5-Trisphosphate Receptors Excitatory Amino Acid Agonist Neurotransmitter Aged Cerebral Cortex Cyclic ADP-Ribose Neurotransmitter Agents Voltage-dependent calcium channel General Neuroscience Glutamate receptor Inositol trisphosphate receptor Middle Aged Acetylcholine Peptide Fragments Cell biology Rats chemistry Biochemistry Receptors Glutamate Metabotropic glutamate receptor Gene Products tat HIV-1 Cholinergic Calcium Female tat Gene Products Human Immunodeficiency Virus Calcium Channels Excitatory Amino Acid Antagonists medicine.drug Cellular/Molecular Synaptosomes |
| Zdroj: | Scopus-Elsevier |
| Popis: | The effect of the human immunodeficiency virus-1 protein Tat was investigated on neurotransmitter release from human and rat cortical nerve endings. Tat failed to affect the release of several neurotransmitters, such as glutamate, GABA, norepinephrine, and others, but it evoked the release of [3H]ACh via increase of cytosolic [Ca2+]. In human nerve terminals, the Tat effect partly depends on Ca2+entry through voltage-sensitive Ca2+channels, because Cd2+halved the Tat-evoked release. Activation of group I metabotropic glutamate receptors (mGluR) and mobilization of Ca2+from IP3-sensitive intraterminal stores are also involved, because the Tat effect was prevented by mGluR antagonists 2-methyl-6-(phenylethynyl)pyridine hydrochloride and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester and by the IP3receptor antagonists heparin and xestospongin C. Furthermore, the group I selective mGlu agonist (RS)-3,5-dihydroxyphenylglycine enhanced [3H]ACh release. In rat nerve terminals, the Tat-evoked release neither depends on external Ca2+ions entry nor on IP3-mediated mechanisms. Tat seems to cause mobilization of Ca2+from ryanodine-sensitive internal stores because its effect was prevented by both 8-bromo-cyclic adenosine diphosphate-ribose and dantrolene. The Tat-evoked release from human synaptosomes was mimicked by the peptide sequences Tat 32-62, Tat 49-86, and Tat 41-60. In contrast, the Tat 49-86 and Tat 61-80 fragments, but not the Tat 32-62 fragment, were active in rat synaptosomes. In conclusion, Tat elicits Ca2+-dependent [3H]ACh release by species-specific intraterminal mechanisms by binding via discrete amino acid sequences to different receptive sites on human and rat cholinergic terminals. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|