Inhibitory effect of polymyxin B on catecholamine secretion from cultured bovine adrenal medullary cells.
Incubation of cultured bovine adrenal medullary cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of Ca2+/phospholipid-dependent protein kinase (protein kinase C), was associated with increased secretion of catecholamine (CA) from the cells. Polymyxin B (PMB, 30-300 microM), a preferential inhibitor of protein kinase C, inhibited the TPA-induced secretion of CA. PMB also inhibited CA secretion induced by other secretagogues, the Ca2+ ionophore ionomycin (10 microM), 56 mM K+ or acetylcholine (ACh). Ionomycin, 56 mM K+ or ACh increased the concentration of intracellular free Ca2+ ([Ca2+]i) (measured using the fluorescent calcium indicator quin2), whereas TPA did not increase [Ca2+]i. PMB blocked the increase in [Ca2+]i induced by 56 mM K+ or ACh at concentrations similar to those inhibiting the secretion of CA. In contrast, PMB did not affect ionomycin-induced increase in [Ca2+]i. These results strongly suggest that CA secretion induced by TPA or ionomycin is mediated via activation of protein kinase C. The results further indicate that in 56 mM K+- or ACh-evoked CA secretion, PMB inhibits the secretion by blocking Ca2+ influx into the cells.
Tachikawa
E
E
Department of Pharmacology, School of Medicine, Iwate Medical University, Morioka, Japan.
Takahashi
S
S
Shimizu
C
C
Ban
H
H
Ohstubo
N
N
Sato
K
K
Kashimoto
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004987:Ethers / Q000494:pharmacology; D015759:Ionomycin; D011112:Polymyxin B / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002395:Catecholamines; D004987:Ethers; D011113:Polymyxins; D015759:Ionomycin; D011112:Polymyxin B; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium