title: Modulation of ultra-low-molecular-weight heparin on [Ca²⁺]i in nervous cells.
abstract: Heparin is an effective competitive antagonist of inositol 1,4,5-trisphosphate receptors (IP(3)Rs). It binds to IP(3)Rs and affects calcium homeostasis. Ultra-low-molecular-weight heparin (ULMWH) is heparin's derivative, the present study was designed to test the effects of ULMWH on intracellular calcium concentration ([Ca(2+)]i) in primary cultured neurons. [Ca(2+)]i was measured by Multilabel Counter Victor-1420 using Fura-2/AM as the calcium fluorescent probe. The results indicated that ULMWH decreased the resting [Ca(2+)]i with or without extracellular Ca(2+). They had no effects on high K(+)-induced elevation of intracellular Ca(2+) level indicating that ULMWH had no effect on external Ca(2+) influx mediated by voltage-dependent calcium channels. However, they partially reduced the increase in [Ca(2+)]i induced by glutamate. Furthermore, ULMWH significantly inhibited the inositol 1,4,5-trisphosphate (IP(3))-induced increase in [Ca(2+)]i both in cellular and subcellular level. These results suggest that ULMWH may reduce [Ca(2+)]i in neurons through suppressing Ca(2+) release from IP(3)-sensitive stores.
authors.affiliation: Pharmacological Institute of New Drugs, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Hao
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Tiangui
authors.initials: T
authors.lastname: Yu
authors.forename: Lihong
authors.initials: L
authors.lastname: Yu
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats
chemical_list: D005456:Fluorescent Dyes; D006495:Heparin, Low-Molecular-Weight; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2