کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815639 | 1058493 | 2010 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
PAC1hop receptor activation facilitates catecholamine secretion selectively through 2-APB-sensitive Ca2+ channels in PC12 cells
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کلمات کلیدی
DMEMIC3LDCVsKrebs-Ringer bufferInsP3BCCsPAC1ICSinositol triphosphatePACAPGPCRKRbCa2+ - Ca2 +cAMP - cAMPG-protein coupled receptor - G-پروتئین همراه گیرندهNa+ - Na +[Ca2+]i - [Ca2 +] iCyclic adenosine monophosphate - آدنوزین مونوفسفات Cyclicadenylate cyclase - آدنیلات سیکلاسDulbecco's modification of Eagle's medium - اصلاح Dulbecco از محیط عقابthird intracellular loop - حلقه درون سلولی سومSodium - سدیم Bovine chromaffin cells - سلول های کروماتین خون گاوendoplasmic reticulum - شبکه آندوپلاسمی cytosolic calcium concentration - غلظت کلسیم سیتوزولintracellular stores - فروشگاه های داخل سلولیpituitary adenylate cyclase activating polypeptide - پلی پپتید فعال کننده adenylate cyclase فعال در هیپوفیزCalcium - کلسیم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
PACAP is a critical regulator of long-term catecholamine secretion from the adrenal medulla in vivo, however the receptor or pathways for Ca2+ entry triggering acute and sustained secretion have not been adequately characterized. We have previously cloned the bovine adrenal chromaffin cell PAC1 receptor that contains the molecular determinants required for PACAP-induced Ca2+ elevation and is responsible for imparting extracellular Ca2+ influx-dependent secretory competence in PC12 cells. Here, we use this cell model to gain mechanistic insights into PAC1hop-dependent Ca2+ pathways responsible for catecholamine secretion. PACAP-modulated extracellular Ca2+ entry in PC12 cells could be partially blocked with nimodipine, an inhibitor of L-type VGCCs and partially blocked by 2-APB, an inhibitor and modulator of various transient receptor potential (TRP) channels. Despite the co-existence of these two modes of Ca2+ entry, sustained catecholamine secretion in PC12 cells was exclusively modulated by 2-APB-sensitive Ca2+ channels. While IP3 generation occurred after PACAP exposure, most PACAP-induced Ca2+ mobilization involved release from ryanodine-gated cytosolic stores. 2-APB-sensitive Ca2+ influx, and subsequent catecholamine secretion was however not functionally related to intracellular Ca2+ mobilization and store depletion. The reconstituted PAC1hop-expessing PC12 cell model therefore recapitulates both PACAP-induced Ca2+ release from ER stores and extracellular Ca2+ entry that restores PACAP-induced secretory competence in neuroendocrine cells. We demonstrate here that although bPAC1hop receptor occupancy induces Ca2+ entry through two independent sources, VGCCs and 2-APB-sensitive channels, only the latter contributes importantly to sustained vesicular catecholamine release that is a fundamental characteristic of this neuropeptide system. These results emphasize the importance of establishing functional linkages between Ca2+ signaling pathways initiated by pleotrophic signaling molecules such as PACAP, and physiologically important downstream events, such as secretion, triggered by them.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 22, Issue 10, October 2010, Pages 1420-1426
Journal: Cellular Signalling - Volume 22, Issue 10, October 2010, Pages 1420-1426
نویسندگان
Tomris Mustafa, James Walsh, Maurizio Grimaldi, Lee E. Eiden,