Norepinephrine-mediated Regulation of 5HT1 Receptor Functioning in Human Platelets

• Published in: Neurochemical research 2008-07, Vol.33 (7), p.1292-1300
• Main Authors: Trincavelli, M. L., Cuboni, S., Montali, M., Santaguida, S., Lucacchini, A., Martini, C.
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Adrenergic alpha-Antagonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blood Platelets - drug effects; Blood Platelets - metabolism; Cell Biology; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - physiology; Data Interpretation, Statistical; Enzyme Inhibitors - pharmacology; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Humans; In Vitro Techniques; Kinetics; Neurochemistry; Neurology; Neurosciences; Norepinephrine - pharmacology; Original Paper; Phentolamine - pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphorylation - drug effects; Propranolol - pharmacology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Receptors, G-Protein-Coupled - metabolism; Receptors, Serotonin, 5-HT1 - blood; Receptors, Serotonin, 5-HT1 - drug effects
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-007-9582-8

Adaptive changes in serotonergic 5HT 1 receptor signalling are believed to underlie the therapeutic effectiveness of antidepressant drugs. Since cells are continuously exposed to neurotransmitters/neuromodulators, spatially and temporally integrated, the responsiveness of a receptor system is dependent upon the physio-pathological state of the cell and the interaction between different neurotransmitters. In the present work, we investigated heterologous regulation of 5HT 1 receptors induced by norepinephrine (NE) in human platelets. NE platelet treatment induced a time and concentration dependent 5HT 1 receptor desensitisation mediated by both alpha and beta receptors through activation of intracellular protein kinases. In particular NE, through PKC activation, regulated 5HT 1 receptor phosphorylation on threonine residues, causing in turn serotonin receptor-G protein uncoupling and functional responsiveness drop. These results suggest that high NE levels (released i.e. during stress disorders) may play an important role in regulating the 5HT 1 responsiveness and in controlling effectiveness of drugs acting on these neurotransmitter systems.