Selective inhibition of cholinergic receptor-mediated /sup 45/Ca++ uptake and catecholamine secretion from adrenal chromaffin cells by taxol and vinblastine

Journal Article · Mon Oct 01 00:00:00 EDT 1984 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5948032

McKay, D B; Schneider, A S

The authors have characterized the actions of taxol, a novel drug promoting microtubule formation, on /sup 45/Ca++ uptake and catecholamine release by isolated and cultured bovine adrenal chromaffin cells. The effects of taxol are compared with corresponding actions of vinblastine. Measurements have also been made of the effects of microtubule-active drugs on the dynamic pattern of release by means of column perifusion of isolated chromaffin cells. Taxol inhibits acetylcholine-stimulated catecholamine secretion (IC50: approximately 1 microM) and /sup 45/Ca++ uptake. The inhibitory effects of both taxol and vinblastine on secretion are rapid in onset (approximately 1 min) and reversible. Taxol and vinblastine (5 microM) exert little or no inhibitory effect on catecholamine secretion induced by 1) the nonreceptor mediated secretagogues K+, Ba++ or veratridine or by 2) the receptor-mediated secretagogues histamine or bradykinin. Similarly, taxol and vinblastine had no effect on K+-induced /sup 45/Ca++ uptake into chromaffin cells. The inhibitory effects of taxol and vinblastine during a secretory challenge are specific for cholinergic receptor-mediated /sup 45/Ca++ uptake and catecholamine release and prevent receptor-mediated membrane depolarization. These results do not support a role for microtubules either in the exocytosis event or in granule transport during an initial secretory challenge. The results would be consistent with either an interaction of microtubule protein with the acetylcholine receptor or a direct action of the drugs on the acetylcholine receptor.

• Research Organization: Sloan-Kettering Inst. for Cancer Research, New York, NY
• OSTI ID: 5948032
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Vol. 231:1
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTINEOPLASTIC DRUGS
BIOCHEMISTRY
CALCIUM 45
UPTAKE
CATECHOLAMINES
ADRENAL GLANDS
ANIMAL CELLS
CALCIUM COMPOUNDS
CATIONS
COMPARATIVE EVALUATIONS
DOSE-RESPONSE RELATIONSHIPS
IN VITRO
INHIBITION
POTASSIUM COMPOUNDS
RECEPTORS
TRACER TECHNIQUES
VINBLASTINE
ALKALI METAL COMPOUNDS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ALKALOIDS
AMINES
ANTIMITOTIC DRUGS
AROMATICS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CHARGED PARTICLES
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DRUGS
ENDOCRINE GLANDS
EVEN-ODD NUCLEI
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
INTERMEDIATE MASS NUCLEI
IONS
ISOTOPE APPLICATIONS
ISOTOPES
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PYRROLES
RADIOISOTOPES
550201* - Biochemistry- Tracer Techniques