Involvement of protein kinase C in the presynaptic nicotinic modulation of [(3)H]-dopamine release from rat striatal synaptosomes
| Autor: | L, Soliakov, S, Wonnacott |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Cyanobacteria Toxins Microcystins Dopamine Bacterial Toxins Enzyme Activators In Vitro Techniques Receptors Nicotinic Receptors Presynaptic Tritium Corpus Striatum Rats Rats Sprague-Dawley Phorbol Esters Papers Animals Calcium Drug Interactions Marine Toxins Enzyme Inhibitors Protein Kinase C Synaptosomes Tropanes |
| Zdroj: | British journal of pharmacology. 132(3) |
| ISSN: | 0007-1188 |
| Popis: | 1. Presynaptic nicotinic ACh receptors modulate transmitter release in the brain. Here we report their interactions with protein kinase C (PKC) with respect to [(3)H]-dopamine release from rat striatal synaptosomes, monitored by superfusion. 2. Two specific PKC inhibitors, Ro 31-8220 (1 microM) and D-erythro-sphingosine (10 microM) significantly reduced (by 51 and 26% respectively) [(3)H]-dopamine release stimulated by anatoxin-a (AnTx), a potent and selective agonist of nicotinic ACh receptors. The inactive structural analogue of Ro 31-8220, bisindolylmaleimide V (1 microM) had no effect. 3. Two phorbol esters, PDBu (1 microM) and PMA (1 microM) potentiated AnTx-evoked [(3)H]-dopamine release by 50 - 80%. This was Ca(2+)-dependent and prevented by PKC inhibitors. In the absence of nicotinic agonist, phorbol esters enhanced basal release through a PKC-independent mechanism. 4. A (86)Rb(+) efflux assay of nicotinic ACh receptor function confirmed that Ro 31-8220 has no nonspecific effect on presynaptic nicotinic ACh receptors. 5. These results suggest that PKC is activated by nicotinic ACh receptor stimulation and mediates a component of AnTx-evoked [(3)H]-dopamine release. In addition, independent activation of PKC can further amplify the response, offering a potential mechanism for receptor crosstalk. |
| Databáze: | OpenAIRE |
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