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Stimulation of the P 2Y Purinergic Receptor on Type 1 Astroglia Results in Inositol Phosphate Formation and Calcium Mobilization
Author(s) -
Helen C.,
Kastritsis C.,
Salm A. K.,
McCarthy Ken
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb11339.x
Subject(s) - purinergic receptor , calcium , inositol phosphate , inositol , receptor , stimulation , inositol trisphosphate , endocrinology , calcium in biology , second messenger system , biology , medicine , adenosine triphosphate , p2y receptor , inositol trisphosphate receptor , chemistry , biochemistry
Cultured astroglia express purinergic receptors that initiate phosphoinositide metabolism and calcium mobilization. Experiments were conducted to characterize the purinergic receptor subtype on type 1 astroglia responsible for stimulating these second‐messenger systems. Inositol phosphate (IP) accumulation and calcium mobilization were measured after stimulation with ATP or purinergic receptor subtype‐selective ATP analogues. ATP (10 –5 M ) increased IP accumulation severalfold. Dose–effect assays monitoring astroglial IP accumulation revealed the order of potency that defines the P 2Y receptor: 2‐methylthioadenosine 5′‐triphosphate > ATP > αβ‐methyleneadenosine 5′‐triphosphate > βγ‐methyleneadenosine 5′‐triphosphate. The influence of ATP on intracellular calcium levels in individual type 1 astroglia was examined using the calcium indicator dye, fura‐2. Dose–effect experiments indicated that ATP was equally potent for generating inositol phosphates and increasing cellular calcium. The most prevalent response (87% of total responses) to ATP consisted of a rapid increase in calcium to a peak level that was approximately five times greater than the prestimulation level. This peak was followed by a decline to a plateau level that was significantly above baseline. This plateau phase of the calcium increase was maintained for at least 5 min in the presence of ATP and was dependent on external calcium. Many (23%) astroglia exhibited spontaneous calcium oscillations whose frequency and magnitude increased after the addition of 10 –5 M ATP. Immunocytochemical staining indicated that the responses occurred in glial fibrillary acidic protein positive cells. We conclude that type 1 astroglia express the P 2Y purinergic receptor which regulates IP production and calcium mobilization.