α2-Adrenoceptor mediated inhibition of exoyctotic noradrenaline release in the absence of extracellular Ca2+
| Autor: | Georg Hertting, Hauke Rensing, Rolf Jackisch, Dorothee Lauth, Clemens Allgaier, Hua Yu Huang |
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| Rok vydání: | 1992 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class chemistry.chemical_element In Vitro Techniques Biology Calcium Ligands Inhibitory postsynaptic potential Hippocampus Peptides Cyclic Clonidine Exocytosis omega-Conotoxins Norepinephrine chemistry.chemical_compound Internal medicine medicine Extracellular Animals 4-Aminopyridine Nerve Endings Pharmacology Antagonist Receptors Adrenergic alpha Calcium Channel Blockers Axons Rats EGTA Endocrinology chemistry Rabbits Amifampridine Extracellular Space Intracellular Homeostasis Signal Transduction |
| Zdroj: | European Journal of Pharmacology: Molecular Pharmacology. 226:245-252 |
| ISSN: | 0922-4106 |
| DOI: | 10.1016/0922-4106(92)90068-7 |
| Popis: | The effect of the α2-adrenoceptor agonist clonidine on 3,4-diaminopyridine (3,4-DAP)-evoked [3H]noradrenaline ([3H]NA) release in rat hippocampus slices was studied in the presence or absence ( + 1 mM EGTA) of extracellular Ca2+. 3H overflow (consisting mainly of unmetabolized [3H]NA) was evoked by addition of 100 μM 3.4-DAP for 10 min to the medium, which always contained 1 μM desipramine. Ligands for L-type voltage-sensitive Ca2+ channels (VSCC) did not affect and evoked [3H]NA release, whereas the preferential N-type VSCC antagonist ω-conotoxin was inhibitory, both in the presence and even more potently in the absence of Ca2+, suggesting an involvement on N-type VSCC in the mechanism of 3,4-DAP-evoked [3H]NA release. In the absence of extracellular Ca2+ the initial influx, which has been previously proposed to liberate Ca2+ from intracellular stores for the exocytotic process, most probably occurs via N-type VSCC. Clonidine inhibited the 3,4-DAP-evoked [3H]NA release in a concentration-dependent manner, both in the presence and even more potently in the absence of Ca2+: its effects were antagonized by yohimbinc. In the presence of extracellular Ca2+ the clonidine effect was not changed by addition of ω-conotoxin. Similar effects of clonidine were found in slices from the rabbit hippocampus. Since the availability of Ca2+ from intracellular stores seems to predominate in the present model, our results lend some support to the suggestion that α2-adrenoceptor activation might affect intracellular mechanisms of Ca2+ homeostasis. On the other hand, however, the present data cannot completely exclude that α2-autoreceptor activation leads to opening of presynaptic K+ channels, or that modulation of Ca2+ influx through VSCC is involved. |
| Databáze: | OpenAIRE |
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