Relationship of dihydropyridine binding sites with calcium-dependent neurotransmitter release in synaptosomes.
In the present work, we have studied the effect of ruthenium red (RuR), La3+ and 4-aminopyridine (4-AP) on the specific binding of (+)-[3H]PN200-110 to synaptosomes, as well as the effect of nitrendipine, nifedipine, and BAY K 8644 on gamma-[3H]aminobutyric acid [( 3H]GABA) release induced by potassium depolarization and by 4-AP in synaptosomes. Scatchard plots indicated that neither RuR nor 4-AP modifies the KD and Bmax of [3H]PN200-110 specific binding, whereas La3+ decreased the Bmax by about 25%; when the effect of the drugs on the total binding of PN200-110 was studied, a similar inhibition by La3+ was found. The calcium antagonists, nitrendipine and nifedipine, did not affect at all the potassium-stimulated release of [3H]GABA nor its release induced by 4-AP. The calcium agonist BAY K 8644 failed to affect both the spontaneous and the potassium-stimulated GABA release. Our results suggest that the binding sites of dihydropyridines in presynaptic membranes are not related to the calcium channels involved in neurotransmitter release with which RuR, La3+, and 4-AP interact.
Massieu
L
L
Departamento de Neurociencias, Universidad Nacional Autónoma de México, D.F., México.
Tapia
R
R
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology; D017275:Isradipine; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010069:Oxadiazoles / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012430:Ruthenium Red / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000631:Aminopyridines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D007473:Ion Channels; D018377:Neurotransmitter Agents; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D012430:Ruthenium Red; D005680:gamma-Aminobutyric Acid; D007811:Lanthanum; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D015761:4-Aminopyridine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D017275:Isradipine