CISPLATIN, AN ANTINEOPLASTIC DRUG, INHIBITS CATECHOLAMINE SECRETION FROM BOVINE ADRENAL CHROMAFFIN CELLS

Long-term pretreatment (12-120 h) of cultured bovine adrenal chromaffi n cells with cis-diamminedichloroplatinum (cisplatin, Pt(NH3)2Cl2) (33 muM), an antineoplastic drug, resulted in a decrease in the secretion of catecholamines from the cells stimulated by acetylcholine. Acetylc holine-induced Ca-45(2+) influx into the cells was also reduced in the cells pretreated with cisplatin for 48 h. The concentration-response curves (3-66 muM) for cisplatin inhibition of the secretion and Ca-45( 2+) influx were quite similar. Pretreatment of cells with 33 muM Pt4or carboplatin, an analog of cisplatin, for 48 h also led to a decreas e in acetylcholine-evoked secretion, but not with 33 muM Pt2+ or other metals (Au+, Au3+, Ni2+, OS3+, Pd2+, Ir3+, and Ir4+) that have proper ties similar to Pt4+. These results strongly suggest that in bovine ad renal chromaffin cells, cisplatin (3-66 muM) inhibits catecholamine se cretion by the suppression of the Ca2+ influx into the cells evoked by acetylcholine and that the inhibitory effect of cisplatin is attribut able to the tetravalent platinum ion in its molecule.