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.
Tachikawa
E
E
Department of Pharmacology, School of Medicine, Iwate Medical University, Morioka, Japan.
Yoshinari
H
H
Takahashi
S
S
Kashimoto
T
T
Mizuma
K
K
Takahashi
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008670:Metals / Q000494:pharmacology
D002395:Catecholamines; D008670:Metals; D000109:Acetylcholine; D002945:Cisplatin; D002118:Calcium