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 μM) 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 μM), 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 reflects 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.