RT Journal Article
SR Electronic
T1 Nongenomic Regulation of the Kinetics of Exocytosis by Estrogens
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 631
OP 637
DO 10.1124/jpet.301.2.631
VO 301
IS 2
A1 José D. Machado
A1 Carmen Alonso
A1 Araceli Morales
A1 José F. Gómez
A1 Ricardo Borges
YR 2002
UL http://jpet.aspetjournals.org/content/301/2/631.abstract
AB The role of nongenomic action of estrogens on elicited catecholamine secretion and exocytosis kinetics was studied in perfused rat adrenals and in cultured bovine chromaffin cells. 17β-Estradiol as well as the estrogen receptor modulators raloxifene and LY117018, but not 17α-estradiol, inhibited at the micromolar range the catecholamine output elicited by acetylcholine or high potassium. However, these agents failed to modify the secretion elicited by high Ca2+ in glands treated with the ionophore A-23187 (calcimycin), suggesting that estrogens did not directly act on the secretory machinery. At the single cell level, estrogens modified the kinetics of exocytosis at nanomolar range. All of the drugs tested except 17α-estradiol produced a profound slowing down of the exocytosis as measured by amperometry. LY117018 also reduced the granule content of catecholamines. 17β-Estradiol reduced the intracellular free Ca2+ but only at micromolar concentrations, whereas nanomolar concentrations increased the cAMP levels. These effects were reproduced with the nonpermeable drug 17β-estradiol-horseradish peroxidase and antagonized with nanomolar concentrations of the antiestrogen ICI 182,780 (fulvestrant). Our data suggest the presence of membrane sites that regulate both the exocytotic phenomenon and the total catecholamine release with high and low affinity, respectively. The American Society for Pharmacology and Experimental Therapeutics