Involvement of protein kinase C in the presynaptic nicotinic modulation of [(3)H]-dopamine release from rat striatal synaptosomes..
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.
Soliakov
L
L
Department of Biology & Biochemistry, University of Bath, Bath BA2 7AY.
Wonnacott
S
S
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology; D052998:Microcystins; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium; D014326:Tropanes
D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D010703:Phorbol Esters; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; D014326:Tropanes; D014316:Tritium; C509783:anatoxin a; D011493:Protein Kinase C; D002118:Calcium; D004298:Dopamine