Comparison of the effects of antimitotic drugs on alpha-tubulin mRNA, microtubules and nicotinic receptor-mediated catecholamine secretion in adrenal chromaffin cells in culture.
1. Four hour treatments of adrenal chromaffin cells with colchicine (10, 100 microM and 1 mM), tubulozole (10 microM) or podophyllotoxin (100 microM) decreases alpha-tubulin mRNA content. Vinblastine (10 microM) and taxol (10 microM), however, do not decrease alpha-tubulin mRNA content. 2. Immunocytochemical techniques demonstrate that 4 hr treatments with all of the antimitotic drugs (colchicine, podophyllotoxin, taxol, tubulozole and vinblastine) produce abnormal microtubule arrays. 3. The effects of 4 hr treatments with the antimitotic drugs on adrenal catecholamine secretion are all qualitatively the same; each drug selectively inhibits adrenal nicotinic acetylcholine receptor-stimulated catecholamine release, while having no inhibitory actions on release stimulated through noncholinergic mechanisms. 4. These studies demonstrate that autoregulation of tubulin synthesis occurs in cultured adrenal chromaffin cells. 5. All of the antimitotic drugs selectively inhibit nicotinic receptor-mediated adrenal catecholamine release under treatment conditions that affect adrenal microtubules. These results support the possibility that the actions of the antimitotic drugs on adrenal nicotinic receptors may involve microtubules.
Gu
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H
Division of Pharmacology, Ohio State University, College of Pharmacy, Columbus 43210.
McKay
S B
SB
Burkman
A M
AM
McKay
D B
DB
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D007150:Immunohistochemistry; D008870:Microtubules / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014404:Tubulin / Q000235:genetics*
D000970:Antineoplastic Agents; D002395:Catecholamines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014404:Tubulin