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Coupling of Astroglial α 2 ‐Adrenoreceptors to Second Messenger Pathways
Author(s) -
Enkvist M. O. Kristian,
Hämäläinen Heli,
Jansson Christian C.,
Kukkonen Jyrki P.,
Hautala Rasmus,
Courtney Michael J.,
Åkerman Karl E. O.
Publication year - 1996
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 - 10.1046/j.1471-4159.1996.66062394.x
Subject(s) - rauwolscine , second messenger system , biology , phospholipase c , receptor , medicine , endocrinology , receptor antagonist , pertussis toxin , inositol phosphate , inositol , forskolin , agonist , antagonist , g protein , microbiology and biotechnology , yohimbine , biochemistry
We have investigated which α 2 ‐receptor subtypes are expressed in cultured cortical astroglia, and their coupling to second messengers. Binding assays using [ 3 H]rauwolscine showed a very low number of α 2 receptors in the astrocytic cultures. Treatment of cultures with dibutyryl cyclic AMP (dBcAMP) increased significantly the number of receptors. The RNase protection assay was used to investigate which receptor subtype the cells express. The α 2B message was expressed at a low level in both treated and untreated cells, the levels of mRNA for the α 2A/D subtype were up‐regulated significantly in cells treated with dBcAMP and no expression of mRNA for the α 2C subtype was detected. The α 2 agonist dexmedetomidine inhibited forskolin‐induced increases in cyclic AMP both in treated and untreated cultures in a pertussis toxin‐dependent manner. This effect was abolished by the α 2 ‐receptor antagonist rauwolscine. Selective α 2 ‐receptor agonists dexmedetomidine, clonidine, and UK14,304 all increased intracellular calcium only in dBcAMP‐treated cells. The antagonist rauwolscine abolished this effect. Ca 2+ responses were also seen in the absence of extracellular Ca 2+ and they were inhibited by the phospholipase C inhibitor U‐73122, suggesting that astroglial α 2 receptors are coupled to the inositol phospholipid pathway. We therefore also tested the effect of dexmedetomidine directly on inositol 1,4,5‐trisphosphate accumulation. A significant increase was seen that was blocked by the antagonist rauwolscine and, as expected, by U‐73122. In short, the results demonstrate that the α 2 receptors in astroglia are coupled to multiple second messenger pathways. They are up‐regulated in cells treated with dBcAMP, which simultaneously assume a process‐bearing morphology. If this morphological change reflects some in vivo process such as reactive gliosis, the up‐regulation of α 2 ‐receptor expression could mean an adaptive change in astrocytic responses to a common neurotransmitter, noradrenaline.