Modulation of [3H]serotonin release by dihydropyridines in spinal cord synaptosomes.
The release of [3H]monoamines from preloaded synaptosomes from spinal cord is K(+)-dependent and can be modulated by L-type Ca2+ channel agonists such as the 1,4-dihydropyridine (1,4-DHP), Bay K 8644. Whereas the basal release of [3H]monoamines was not altered by Bay K 8644, K(+)-stimulated release of [3H]norepinephrine was enhanced 35% and [3H]serotonin 50%. Modulation of release by Bay K 8644 was dependent on the K+ concentration in the medium, being present only at submaximal depolarization with 15 mM K+. Enhanced release in the presence of Bay K 8644 was concentration-dependent and Ca2(+)-dependent. Ca2(+)-independent release induced by fenfluramine was not enhanced by Bay K 8644. Both nimodipine and nitrendipine, 1,4-DHP antagonists, produced a concentration-dependent block of the Bay K 8644-induced monoamine release and had no independent effect on basal or K(+)-stimulated release. omega-Conotoxin GVIA (omega-CgTx) produced a concentration dependent decrease of K(+)-stimulated serotonin release, which antagonized the stimulatory effect of low concentrations of Bay K 8644. However, omega-CgTx did not alter the enhancement of K(+)-stimulated release at higher concentrations of Bay K 8644. The data from the present work establish the conditions for modulation of K(+)-evoked monoamine release in spinal cord by 1,4-DHP agonists and suggest a role for the L-type voltage dependent Ca2+ channel in this process.
Department of Anesthesiology, University of Texas Health Science Center, San Antonio 78284-7838.
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Gandhi
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Jones
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D004095:Dihydropyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D008978:Mollusk Venoms; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D012701:Serotonin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA; D011188:Potassium