The aim of the present study was to investigate the possible role played by the Na+-Ca2+ exchange system in the modulation of [3H]dopamine ([3H]DA) release from tuberoinfundibular hypothalamic (TIDA) neurons. 2′,4′-Dimethylbenzamil (DMB) dose-dependently (10-100 μM) inhibited Na+-dependent 45Ca2+ efflux from brain synaptosomes. This compound (30-300 μM), as well as α-phenylbenzamil amiloride (30-100 μM), another inhibitor of the Na+-Ca2+ antiporter, was also able to stimulate basal release of [3H]DA from superfused TIDA neurons. This stimulation was completely prevented by the removal of extracellular Ca2+ ions, in the presence of 1 mM ethylene glycol bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid. In addition, DMB-induced [3H]DA release was unaffected by the dopamine transport inhibitor nomifensine (10 μM). On the other hand, 5-[N-methyl-N-guanidinocarbonylmethyl]amiloride (MGCMA) (100-300 μM), which lacks inhibitory properties on the Na+-Ca2+ exchanger but behaves as an inhibitor of the Na+-H+ antiporter, failed to modify basal [3H] DA release from TIDA neurons. When the Na+-Ca2+ antiporter operates as a Ca2+ influx pathway, as occurs upon the removal of extracellular Na+ ions, Na+-dependent 45Ca2+ uptake in brain synaptosomes was dose-dependently (10-300 μM) inhibited by DMB, whereas DMB itself was unable to prevent 55 mM K+-induced 45Ca2+ uptake, which mainly reflects the activation of voltage-operated Ca2+ channels. In keeping with these results, ouabain (500 μ-induced [3H]DA release, which depends on the activation of the Na+-Ca2+ exchanger due to inhibition of the Na+-K+-ATPase pump, was prevented by superfusion of TIDA neurons with DMB (50 μM). By contrast, MGCMA (100 μM) failed to modify either Na+-dependent 45Ca2+ influx or ouabain-induced [3H]DA release. In conclusion, the results of the present study appear to suggest that the pharmacological inhibition of the Na+-Ca2+ antiporter by amiloride analogues may affect DA release from central neurons. Opposite effects are observed, depending on the direction of operation of the exchanger. In fact, when the Na+-Ca2+ exchanger operates as a Ca2+ efflux pathway, its pharmacological blockade can produce a stimulation of DA release. In contrast, when this antiporter operates as a Ca2+ influx pathway, as occurs as a consequence of the inhibition of the Na+-K+-ATPase pump by ouabain, its pharmacological blockade can prevent ouabain-induced DA release from TIDA neurons.
|Number of pages||8|
|Publication status||Published - Sep 1990|
ASJC Scopus subject areas