scholarly journals Adrenergic Receptor Function in Panic Disorder, I. Platelet α2 Receptors Gi Protein Coupling, Effects of Imipramine, and Relationship to Treatment Outcome

1999 ◽  
Vol 20 (2) ◽  
pp. 162-176 ◽  
Author(s):  
G Gurguis
CHEST Journal ◽  
1981 ◽  
Vol 80 (1) ◽  
pp. 61S-63S ◽  
Author(s):  
Roy Thomas McKay ◽  
Stuart M. Brooks ◽  
Carl Johnson

2002 ◽  
Vol 7 (3) ◽  
pp. 134-141 ◽  
Author(s):  
Norman B Schmidt ◽  
Helen T Santiago ◽  
John H Trakowski ◽  
J Michael Kendren

OBJECTIVE:Although there has been a link between certain types of pain, notably chest pain, and panic disorder, the relation between pain and panic disorder has not been systematically evaluated. In the present study, the relation between pain symptoms (headache, chest pain, stomach pain, joint pain) and the clinical presentation of patients with panic disorder was evaluated.HYPOTHESES:Pain was generally hypothesized to be related to increased symptoms of anxiety, panic-relevant cognitive domains and treatment outcome. In terms of specific pain domains, headache and chest pain were expected to be more closely related to anxiety-related symptoms.PARTICIPANTS AND METHODS:Patients (n=139) meeting the criteria of theDiagnostic and Statistical Manual of Mental Disorders - Fourth Editionfor panic disorder completed a set of standardized clinician-rated and self-reported measures. Moderator analyses were used in a subset of these patients completing a treatment outcome study.RESULTS:Approximately two-thirds of the participants endorsed at least one current pain symptom. The hypotheses were partially supported, with pain being associated with higher levels of anxiety and depression symptoms, as well as panic frequency. Pain was also related to several cognitive features, including anxiety sensitivity and panic appraisals. Headache and chest pain were more highly associated with anxiety symptoms than was joint pain. Cognitive measures did not mediate the relation between anxiety and pain, and pain did not significantly moderate outcome in response to cognitive-behavioural therapy.CONCLUSIONS:Co-occurring pain symptoms appear to be more highly related to phenomenology than to treatment response in patients with panic disorder.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Anita Sahu ◽  
Sromona D Mukherjee ◽  
Conner P Witherow ◽  
Kate Stenson ◽  
John Tesmer ◽  
...  

Insulin impairs β2-adrenergic receptor (β2AR) function via trans-phosphorylation through G protein-coupled receptor kinase 2 (GRK2). However, less is known about dephosphorylation mechanisms mediated by protein phosphatase 2A (PP2A) during this insulin-β2AR cross-talk. Pharmacologic or genetic inhibition of phosphoinositide 3-kinase γ (PI3Kγ) unexpectedly resulted in significant reduction of insulin-mediated β2AR phosphorylation. Interestingly, β2AR-associated phosphatase activity was inhibited by insulin but was reversed by knock-down of PI3Kγ showing negative regulation of PP2A by PI3Kγ. Co-immunoprecipitation and surface plasmon resonance studies using purified proteins showed that GRK2 and PI3Kγ form a complex and could be recruited to β2ARs as GRK2 interacts with insulin receptor substrate (IRS) following insulin treatment. Further, co-immunoprecipitation studies showed that PI3Kγ directly interacted with both IRS-1 and IRS-2 but only IRS-2 interaction with PI3Kγ significantly increased following insulin stimulation. These results indicated that PI3Kγ could also be directly recruited to the receptor complex by IRS-2. Consistently, β-blocker pretreatment did not reduce insulin-mediated β2AR phosphorylation indicating agonist- and Gβγ-independent non-canonical regulation of receptor function. Mechanistically, PI3Kγ inhibits PP2A activity at the βAR complex by phosphorylating an intracellular inhibitor of PP2A (I2PP2A). Knock-down or CRISPR ablation of endogenous I2PP2A unlocked PP2A inhibition mediating β2AR dephosphorylation showing an unappreciated acute regulation of PP2A in mediating insulin-β2AR cross-talk.


Sign in / Sign up

Export Citation Format

Share Document