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 04:00:00 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), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 231:1; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

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