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Serotonin-2A receptors and its signal transduction in brains and platelets of Wistar-Zagreb 5HT rats

The postsynaptic serotonin-2A (5HT-2A), receptors mediate a number of central and peripheral 5HT functions and have a role in several psychiatric disorders. 5HT-2A receptor is directly coupled to the phosphoinositide signalling system and its activation finally give rise to the intracellular calcium [Ca2+], resulting in phosphorylation/dephosphorylation of protein substrates. 5HT-2A receptors are disitributed with higest densities in brain cortex but also on blood platelets, which are studied as a potential model of membrane-related neuronal functions as well signal transduction mechanisms. The aim of the present study was to measure reactivity of 5HT-2A signal transduction system, by measuring intracellular  Ca2+ following its 5HT-induced mobilization, in rat sublines with constitutionally altered serotonin homeostasis (Wistar-Zagreb 5HT rats ; obtained by directed selective breeding for extremes in the activity of platelet 5HT transporter). Previous studies on 5HT-2A receptor kinetics and 5HT-2A mRNA expression did not show significant differences between the sublines. Fura– 2 fluorescent indicator was used for measuring intarcellular [Ca2+] in platelet-rich-plasma and frontal cortex membranes, simultaneously on animals from both sublines of Wistar-Zagreb 5HT rats. Ca2+ concentration was measured basally and after 5HT-induced Ca2+ mobilization. Sublines of Wistar-Zagreb 5HT rats showed differences in basal intracellular [Ca2+] in both, brains and platelets. Differences between sublines in [Ca 2+] after stimulation of 5HT-2A receptors by serotonin were observed only in platelets, and not in cortical membranes. Constitutionally altered serotonin homeostasis in Wistar-Zagreb 5HT rats resulted in differences in basal intracellular Ca2+ level between sublines, indicating alterations in intracellular signaling of 5HT-2A receptor. Different calcium signalization after stimulation of receptors by 5HT indicates altered functional response of 5HT-2A receptor, at least in platelets.

5HT-2A receptor; calcium; Wistar-Zagreb 5HT rat; serotonin homeostasis

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