Refine
Has Fulltext
- yes (7)
Is part of the Bibliography
- yes (7)
Document Type
- Journal article (5)
- Doctoral Thesis (2)
Keywords
- anxiety (3)
- chronic heart failure (2)
- depression (2)
- myocardial infarction (2)
- Einwärtsgleichrichtung (1)
- G Protein (1)
- G beta gamma (1)
- G protein coupled receptor (1)
- G-Protein gekoppelte Rezeptoren (1)
- GIRK (1)
Institute
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (5)
- Institut für Pharmakologie und Toxikologie (3)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (2)
- Medizinische Klinik und Poliklinik I (2)
- Comprehensive Cancer Center Mainfranken (1)
- Institut für Organische Chemie (1)
- Institut für Virologie und Immunbiologie (1)
- Neurochirurgische Klinik und Poliklinik (1)
- Neurologische Klinik und Poliklinik (1)
- Physiologisches Institut (1)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 232944 (1)
Proteolytic cleavage of the extracellular domain affects signaling of parathyroid hormone 1 receptor
(2022)
Parathyroid hormone 1 receptor (PTH1R) is a member of the class B family of G protein-coupled receptors, which are characterized by a large extracellular domain required for ligand binding. We have previously shown that the extracellular domain of PTH1R is subject to metalloproteinase cleavage in vivo that is regulated by ligand-induced receptor trafficking and leads to impaired stability of PTH1R. In this work, we localize the cleavage site in the first loop of the extracellular domain using amino-terminal protein sequencing of purified receptor and by mutagenesis studies. We further show, that a receptor mutant not susceptible to proteolytic cleavage exhibits reduced signaling to G\(_s\) and increased activation of G\(_q\) compared to wild-type PTH1R. These findings indicate that the extracellular domain modulates PTH1R signaling specificity, and that its cleavage affects receptor signaling.
Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.