کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9002076 | 1118571 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Azaspiracid-4 inhibits Ca2+ entry by stored operated channels in human T lymphocytes
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کلمات کلیدی
Thapsigargin9-(tetrahydro-2-furanyl)-9H-purin-6-amineAzaspiracidMTXdbcAMPforskolinAzaspiracidsFskPSScAMP - cAMP[Ca2+]i - [Ca2 +] iadenosine 3′,5′-cyclic monophosphate - آدنوزین 3 '، 5'-سیکلیک منوفسفرهphysiological saline solution - راه حل فیزیولوژیکی شورSOC - سیستم روی یک تراشهcytosolic calcium concentration - غلظت کلسیم سیتوزولLymphocytes - لنفوسیت هاMaitotoxin - مایتوتوکسینCalcium channel - کانال کلسیمcytosolic calcium - کلسیم سیتوزول
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Azaspiracids (AZs) are a new group of phycotoxins discovered in the Ireland coast that includes the isolated analogues: AZ-1, AZ-2, AZ-3, AZ-4 and AZ-5 and the recently described AZ-6-11. Azaspiracid toxic episodes show gastrointestinal illness, but neurotoxic symptoms are also observed in mouse bioassay. Despite their great importance in human health, so far its mechanism of action is largely unknown. In this report, we present the first data about the effect of AZ-4 on cytosolic calcium concentration [Ca2+]i in freshly human lymphocytes. Cytoslic Ca2+ variations were determined by fluorescence digital imaging microscopy using Fura2 acetoxymethyl ester (Fura2-AM). AZ-4 did not modify cytosolic Ca2+ in resting cells. However, the toxin dose-dependent inhibited the increase in cytosolic Ca2+ levels induced by thapsigargin (Tg). AZ-4 decreased Ca2+-influx induced by Tg but did not affect the Ca2+-release from internal stores induced by this drug. The effects of AZ-4 on Ca2+-influx induced by Tg were reversible and not regulated by adenosine 3â²,5â²-cyclic monophosphate (cAMP) pathway. When AZ-4 was added before, after or together with nickel, an unspecific blocker of Ca2+ channels, the effects were indistinguishable and additive. AZ-4 also inhibited maitotoxin (MTX)-stimulated Ca2+-influx by 5-10%. Thus, AZ-4 appeared to be a novel inhibitor of plasma membrane Ca2+ channels, affecting at least to store operated channels, showing an effect clearly different from other azaspiracid analogues.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 69, Issue 11, 1 June 2005, Pages 1627-1636
Journal: Biochemical Pharmacology - Volume 69, Issue 11, 1 June 2005, Pages 1627-1636
نویسندگان
Amparo Alfonso, Yolanda Román, Mercedes R. Vieytes, Katsuya Ofuji, Masayuki Satake, Takeshi Yasumoto, Luis M. Botana,