The conditions of Ca2+ entry via L-type channels for induction of serotonin release from rabbit hippocampus.
The L-type voltage-sensitive calcium channel (VSCC) agonists of the dihydropyridine (DHP) type, Bay K 8644 and (+)-202-791, concentration dependently enhanced the K+ (26.2 mM)-induced 5-HT release from slices of rabbit hippocampus prelabelled with [3H]5-HT when the slices were treated with the monoamine oxidase (MAO) inhibitor, pargyline. The DHP agonists were ineffective on K+ (26.2 mM)-induced release in the absence of pargyline. However, when omega-conotoxin GVIA pretreatment of the slices irreversibly blocked N-type VSCCs, (+)-202-791 markedly enhanced the release of 5-HT evoked by 26.2 mM K+. Thus, at this rather strong stimulus intensity either an increase in the (preferentially cytoplasmic) transmitter pool or blockade of N-type VSCCs was necessary in order to unmask agonist-activated L-type VSCCs. Reduction of the depolarization intensity from 26.2 to 17.2 mM K+, given for 8 min, strongly intensified the stimulatory effects of L-type VSCC agonists irrespective of the use of pargyline under these conditions. The concentration-response curve of (+)-202-791 was 'competitively' shifted to the right by the enantiomer, (-)-202-791, with a pA2 value of 8.6. In conclusion, N- and L-type VSCCs seem to differ in their relation to the cellular machinery for 5-HT release, the latter getting markedly operative when a weak and sustained depolarization is applied or when N-type VSCCs are blocked or when the cytoplasmic transmitter pool is expanded by inhibition of MAO.
Feuerstein
T J
TJ
Neuropharmakologisches Labor der Neurologischen Universitätsklinik, Freiburg, F.R.G.
Neuschwander
E
E
Sauermann
W
W
Lupp
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008996:Monoamine Oxidase Inhibitors; D010456:Peptides, Cyclic; D011985:Receptors, Serotonin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA; D010293:Pargyline; D011188:Potassium; D002118:Calcium