Effect of different organic and inorganic blockers of calcium entry on the release of endogenous dopamine from tuberoinfundibular neurones

In the present study the effect of different blockers of calcium entry belonging to different chemical classes on basal and K⁺-elicited release of endogenous dopamine (DA) from tuberoinfundibular dopaminergic neurones was studied in vitro. For this purpose fragments of hypothalamus containing arcuate-periventricular nuclei and median eminence were incubated in vitro and endogenous DA released into the medium was assayed by radioenzymatic assay. The organic blockers of calcium entry, nitrendipine, nimodipine, nifedipine, diltiazem and flunarizine did not modify basal or K⁺-evoked release of endogenous DA, unless very large concentrations (100μM) of nifedipine or diltiazem were used. The phenylalkylamine methoxyverapamil (D-600) consistently inhibited K⁺-stimulated release of endogenous DA in concentrations of 50 and 100 μM. Cobalt and lanthanum, two ions with an ionic radius similar to that of calcium and which are known to inhibit calcium fluxes through nerve membranes, significantly blocked release of endogenous DA elicited by 35 mM K⁺. In summary, the results of the present study showed that calcium channels in the tuberoinfundibular dopaminergic system displayed a different sensitivity to various classes of blockers of calcium entry. Inorganic blockers of calcium entry, like lanthanum and cobalt, appeared to be the most effective in blocking Ca²⁺-dependent release of endogenous DA, whereas, among the organic calcium antagonists, phenylalkylamines seemed to possess a certain degree of effectiveness.