Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 86, Issue 15, Pages 3456-3468Publisher
WILEY
DOI: 10.1002/jnr.21784
Keywords
Ca2+ channels; H-1 receptor; histamine; TRP channels; STIM; Orai
Categories
Funding
- National Council for Science and Technology (Conacyt), Mexico
Ask authors/readers for more resources
Glial and glia-derived cells express a variety of receptors for neurotransmitters and hormones, the majority of which evoke both Ca2+ release from intracellular stores and Ca2+ entry across the plasma membrane. We investigated the links between histamine H, receptor activation, Ca2+ release from intracellular stores and Ca2+ influx in human astrocytoma U373 MG cells. Histamine, through a H-1 receptor-mediated effect, evoked an increase in cytoplasmic free calcium concentration ([Ca2+](i)) that occurred in two phases: an initial, transient, increase owing to Ca2+ mobilization from intracellular pools, and a second, sustained increase dependent on both Ca2+ influx and continuous receptor occupancy. The characteristics of histamine-induced increases in [Ca2+](i) were similar to the capacitative entry evoked by emptying of the Ca2+ stores with thapsigargine, and different from that observed when Ca2+ influx was activated with OAG (1-oleoyl-2-acetyl-sn-glycerol), a diacylglycerol (DAG) analog. OAG application or increased endogenous DAG, resulting from DAG kinase inhibition, reduced the histamine-induced response. Furthermore, activation of the DAG target, protein kinase C (PKC), by TPA (12-O-tetradecanoyl 4 beta-phorbol 13 alpha-acetate) resulted in inhibition of the histamine-induced Ca2+ response, an action prevented by PKC inhibitors. By using reverse transcriptase-polymerase chain reaction analysis, mRNAs for transient receptor potential channels (TRPCs) 1, 4, and 6 as well as for STIM1 (stromal-interacting molecule) and Orai1 were found to be expressed in the U373 MG cells, and confocal microscopy using specific antibodies revealed the presence of the corresponding proteins. Therefore, TRPCs may be candidate proteins forming store-operated channels in the U373 MG cell line. Further, our results confirm the involvement of PKC in the regulation of H-1 receptor-induced responses and point out to the existence of a feedback mechanism acting via PKC to limit the increase in [Ca2+](i). (C) 2008 Wiley-Liss, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available