Coupling of Astroglial α2-Adrenoreceptors to Second Messenger Pathways |
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Authors: | M O Kristian Enkvist Heli Hämäläinen Christian C Jansson Jyrki P Kukkonen Rasmus Hautala Michael J Courtney Karl E O Åkerman |
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Institution: | Department of Biochemistry and Pharmacy, Åbo Akademi University, Turku, Finland |
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Abstract: | Abstract: We have investigated which α2-receptor subtypes are expressed in cultured cortical astroglia, and their coupling to second messengers. Binding assays using 3H]rauwolscine showed a very low number of α2 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 α2B message was expressed at a low level in both treated and untreated cells, the levels of mRNA for the α2A/D subtype were up-regulated significantly in cells treated with dBcAMP and no expression of mRNA for the α2C subtype was detected. The α2 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 α2-receptor antagonist rauwolscine. Selective α2-receptor agonists dexmedetomidine, clonidine, and UK14,304 all increased intracellular calcium only in dBcAMP-treated cells. The antagonist rauwolscine abolished this effect. Ca2+ responses were also seen in the absence of extracellular Ca2+ and they were inhibited by the phospholipase C inhibitor U-73122, suggesting that astroglial α2 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 α2 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 α2-receptor expression could mean an adaptive change in astrocytic responses to a common neurotransmitter, noradrenaline. |
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Keywords: | α2-Adrenergic Receptor Astroglia Cyclic AMP Inositol 1 4 5-trisphosphate Ca2+ |
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