The Na(+)-Ca++ exchanger in central nerve endings: the relationship between its pharmacological blockade and dopamine release from tuberoinfundibular hypothalamic neurons.
2', 4'-Dimethylbenzamiloride (DMB), an inhibitor of Na(+)-Ca++ antiporter dose-dependently (10-100 microM) inhibited Na(+)-dependent 45Ca++ efflux from brain synaptosomes. This compound was also able to stimulate basal release of [3H]DA from superfused TIDA neurons. Another amiloride analogue, 5-N-methyl-N-guanidinocarbonylmethylamiloride (MGCMA, 100-300 microM), which lacks of inhibitory properties on the Na(+)-Ca++ antiporter, failed to modify basal [3H]DA release from TIDA neurons. In addition, when the antiporter operates as a Ca(++)-influx pathway, DMB dose-dependently inhibited Na(+)-dependent 45Ca++ uptake in brain synaptosomes, whereas it did not prevent K(+)-induced 45Ca++ uptake, which reflets the activation of voltage-operated Ca++ channels. Finally DMB inhibited ouabain-induced [3H]DA release, which depends on the activation of the Na(+)-Ca++ exchanger due to the inhibition of the Na+/K(+)-ATPase pump.
University of Chieti, Italy.
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Taglialatela
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Di Rienzo
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002794:Choline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D009411:Nerve Endings / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger; D013574:Synaptosomes / Q000378:metabolism
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; C053494:2',4'-dimethylbenzamil; D010042:Ouabain; D000584:Amiloride; D002794:Choline; D011188:Potassium; D002118:Calcium; D004298:Dopamine