Cisplatin, an antineoplastic drug, inhibits catecholamine secretion from bovine adrenal chromaffin cells

Long-term pretreatment (12-120 h) of cultured bovine adrenal chromaffin cells with cis-diamminedichloroplatinum (cisplatin, Pt(NH3)2Cl2) (33 microM), an antineoplastic drug, resulted in a decrease in the secretion of catecholamines from the cells stimulated by acetylcholine. Acetylcholine-induced 45Ca2+ influx into the cells was also reduced in the cells pretreated with cisplatin for 48 h. The concentration-response curves (3-66 microM) for cisplatin inhibition of the secretion and 45Ca2+ influx were quite similar. Pretreatment of cells with 33 microM Pt4+ or carboplatin, an analog of cisplatin, for 48 h also led to a decrease in acetylcholine-evoked secretion, but not with 33 microM Pt2+ or other metals (Au+, Au3+, Ni2+, Os3+, Pd2+, Ir3+, and Ir4+) that have properties similar to Pt4+. These results strongly suggest that in bovine adrenal chromaffin cells, cisplatin (3-66 microM) inhibits catecholamine secretion by the suppression of the Ca2+ influx into the cells evoked by acetylcholine and that the inhibitory effect of cisplatin is attributable to the tetravalent platinum ion in its molecule.