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Journal home Current Issue Advance Online Publication Archive Online sample issue FREE! Author index Keyword index For authors Editorial Board Instructions for authors Aims and scope Indexed in Author queries Online Submission Customer Services Subscription information Journal prices Order sample issue Purchase articles, reprints & permissions Advertising Contact NPG		Neuropsychopharmacology (1996) 15 555-561. -Adrenoceptor-Linked Protein Kinase A (PKA) Activity in Human Fibroblasts from Normal Subjects and from Patients with Major Depression D Hal Manier MS1, Andrea Eiring BS1, Richard C Shelton MD1,2 and Fridolin Sulser MD1,2 1From the Departments of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 2Departments of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee Correspondence: Fridolin Sulser, MD, Vanderbilt University School of Medicine, AA-2232 MCN, Nashville, TN 37232 ABSTRACT Human fibroblasts from normal subjects and from patients with major depression are cultured and their -adrenoreceptor-cyclic AMP-protein kinase A (PKA) system characterized. The results indicate that the -adrenoreceptor-mediated activation of PKA in the 900 g supernatant fraction of human fibroblasts is mediated via -adrenoreceptors. The activation of PKA by isoproterenol is very rapid with maximal stimulation occurring at 5 seconds. The time course of PKA activation by isoproterenol in fibroblasts from patients with major depression is identical to that in fibroblasts from normal subjects but the magnitude of activation is significantly reduced in fibroblasts from patients with major depression. Dose-response curves on cyclic AMP mediated activation of PKA confirmed the previously reported reduction in activation of PKA in patients with major depression but demonstrated that this reduction occurs without a change in the EC50 values of cyclic AMP (approximately 20 nmol/L). The blunted -adrenoceptor-linked PKA responses in patients with major depression occur without a change in the expression of the PKA catalytic subunit C. The studies suggest that the -adrenoceptor-coupled adenylate cyclase PKA system in human fibroblasts may represent a valid model to explore possible abnormalities in the fine tuning of the -adrenergic transduction cascade in patients with affective disorders. Ó American College of Neuropsychopharmacology Keywords: Human fibroblasts; Major depression; Cyclic AMP; Isoproterenol; Protein kinase A (PKA); β-adrenoceptor subtype   top		Article Links  Send to a friend  Download PDF   Next Article   Previous Article   Table of Contents
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