The effect of the ionophores X-537A and A23187 on the noradrenaline output from peripheral adrenergic neurones in the presence of various divalent cations.

1 The effects of the ionophores, X-537A and A23187 on the noradrenaline output from peripheral adrenergic neurones of isolated vas deferens of the guinea-pig were investigated in the presence of various divalent cations.2 X-537A (17 muM) caused an increase in the noradrenaline output in the presence of barium, calcium and strontium. The effectiveness of the cations was Ba > Ca >/= Sr.3 In the absence of calcium and in the presence of ethyleneglycol-bis(2-aminoethylether)-N,N,N',N',-tetraacetic acid (EGTA, 1 mM), the response was reduced by about 50% of that obtained in the presence of calcium.4 Calcium was the most effective cation in stimulating noradrenaline output when reintroduced after pretreatment with A23187 (191 muM). The response increased in an almost linear fashion with the concentration of calcium 1 mM to 10 mM.5 Excess magnesium (20 mM) reduced the response induced by X-537A in the presence of barium. However, it was without effect on the response produced by reintroduction of calcium after pretreatment with A23187.6 The response induced by X-537A in the presence of barium increased with an increase in the concentration of external sodium from 25 mM to 143 mM.7 It is suggested that X-537A may cause an increase in the noradrenaline output by depolarization as well as by transferring cations as an ionophore. On the other hand, A23187 may produce an increase in the noradrenaline output, transferring calcium across the membrane as a specific calcium ionophore.