European Neuropsychopharmacology 12 (2002) 483–487 www.elsevier.com / locate / euroneuro The protein kinase A in platelets from patients with panic disorder a b a a b, * Daniela Tardito , Raffaella Zanardi , Giorgio Racagni , Tiziana Manzoni , Jorge Perez a Center of Neuropharmacology, Department of Pharmacological Sciences, University of Milan, Milan, Italy b Istituto Scientifico HSR, Department of Neuropsychiatry School of Medicine, University Vita-Salute, Milan, Italy Received 12 February 2002; accepted 20 June 2002 Abstract Although previous studies suggested that dysfunctions in the protein kinase A (PKA) and in some of its substrates are associated with several psychiatric disorders, there is no evidence regarding the possible involvement of such components in panic disorder (PD). Thus, the aim of the present study was to investigate the levels of PKA and Rap1 in platelets from patients with such disorder. Twenty-four drug free patients with PD and 24 healthy volunteers participated to the study. Employing the Western Blot analysis, immunostaining and computer-assisted imaging, the levels of the regulatory (R, type I and type II) and the catalytic (C) subunits of PKA, and those of Rap1 were assessed in platelets from the two groups. The data show that patients with PD have significantly higher levels of platelet RI and C subunits of PKA than controls, whereas the levels of RII were unchanged. No significant differences were found in the immunolabelling of Rap1 between groups. These findings may provide clues toward understanding the involvement of cAMP signalling in anxiety disorders.  2002 Elsevier Science B.V./ECNP. All rights reserved. Keywords: Panic disorder; cAMP signalling; PKA; Rap1; Platelets 1. Introduction Panic disorder (PD) is a common mental illness, char- acterized by recurrent panic attacks which consist of The cAMP signalling pathway is implicated in the episodes of intense fear or anxiety accompanied by symp- intracellular events mediated by various neurotransmitters toms of cognitive and autonomic arousal. Epidemiological and neuropeptides. Previous studies have shown that PKA, data of PD have reported lifetime prevalence ranging from a key element of the cAMP signalling, and some of its 1.6 to 3% and a higher risk for females (Weissman et al., substrates are involved in the regulation of motor and 1997). emotive behaviour, memory, stress and also in the action The biochemical mechanism(s) underlying the patho- of psychotropic medications (Abel et al., 1997; Adams et physiology of this disorder remain still unclear. However, al., 1997; Brandon et al., 1998; Silva et al., 2000; Perez et an increasing body of evidence suggests that dysfunctions al., 2000; Feliciello et al., 2001). Furthermore, clinical of neurotransmitters and neuropeptides including mono- investigations have reported that abnormalities in such amines, GABA, acetylcholine and cholecystokinin could components are present in peripheral cells and postmortem be associated with PD (Sullivan et al., 1999; Grove et al., brains of patients with affective disorders (Perez and 1997; Goddard et al., 2001; Battaglia et al., 2001; Kennedy Tardito, 2001; Stewart et al., 2001). et al., 1999). Furthermore, functional alterations in up- stream components of the cAMP signalling as well as lower levels of cAMP have been reported in PD patients *Corresponding author. Current address: IRCCS, Fatebenefratelli, Via (Charney et al., 1989; Maddock et al., 1993; Gurguis et al., Pilastroni 4, 25125 Brescia, Italy. Tel.: 139-030-350-1719; fax: 139- 1997; Marcourakis et al., 2002). Although these alterations 030-353-3513. E-mail address: jperez@oh-fbf.it (J. Perez). may have associated effects on downstream elements of 0924-977X / 02 / $ – see front matter  2002 Elsevier Science B.V./ECNP. All rights reserved. PII: S0924-977X(02)00072-X