TY - JOUR A1 - Giebing, Günter A1 - Tölle, Markus A1 - Jürgensen, Jana A1 - Eichhorst, Jenny A1 - Furkert, Jens A1 - Beyermann, Michael A1 - Neuschäfer-Rube, Frank A1 - Rosenthal, Walter A1 - Zidek, Walter A1 - van der Giet, Markus A1 - Oksche, Alexander T1 - Arrestin-independent internalization and recycling of the urotensin receptor contribute to long-lasting urotensin II - Mediated vasoconstriction N2 - Urotensin II (UII), which acts on the G protein-coupled urotensin ( UT) receptor, elicits long-lasting vasoconstriction. The role of UT receptor internalization and intracellular trafficking in vasoconstriction has yet not been analyzed. Therefore, UII-mediated contractile responses of aortic ring preparations in wire myography and rat UT (rUT) receptor internalization and intracellular trafficking in binding and imaging analyses were compared. UII elicited a concentration-dependent vasoconstriction of rat aorta (-log EC50, mol/L:9.0 +/- 0.1). A second application of UII after 30 minutes elicited a reduced contraction (36 +/- 4% of the initial response), but when applied after 60 minutes elicited a full contraction. In internalization experiments with radioactive labeled VII (I-125-UII), approximate to 70% of rUT receptors expressed on the cell surface of human embryonic kidney 293 cells were sequestered within 30 minutes (half life [t(h)]: 5.6 +/- 0.2 minutes), but recycled quantitatively within 60 minutes (t(h) 31.9 +/- 2.6 minutes). UII- bound rUT receptors were sorted to early and recycling endosomes, as evidenced by colocalization of rUT receptors with the early endosomal antigen and the transferrin receptor. Real-time imaging with a newly developed fluorescent UII (Cy3- UII) revealed that rUT receptors recruited arrestin3 green fluorescent protein to the plasma membrane. Arrestin3 was not required for the endocytosis of the rUT receptor, however, as internalization of Cy3-UII was not altered in mouse embryonic fibroblasts lacking endogenous arrestin2/arrestin3 expression. The data demonstrate that the rUT receptor internalizes arrestin independently and recycles quantitatively. The continuous externalization of rUT receptors provides the basis for repetitive and lasting UII-mediated vasoconstriction Y1 - 2005 SN - 0009-7330 ER - TY - GEN A1 - Deeken, Friederike A1 - Reichert, Markus A1 - Zech, Hilmar A1 - Wenzel, Julia A1 - Wedemeyer, Friederike A1 - Aguilera, Alvaro A1 - Aslan, Acelya A1 - Bach, Patrick A1 - Bahr, Nadja Samia A1 - Ebrahimi, Claudia A1 - Fischbach, Pascale Christine A1 - Ganz, Marvin A1 - Garbusow, Maria A1 - Großkopf, Charlotte M. A1 - Heigert, Marie A1 - Hentschel, Angela A1 - Karl, Damian A1 - Pelz, Patricia A1 - Pinger, Mathieu A1 - Riemerschmid, Carlotta A1 - Rosenthal, Annika A1 - Steffen, Johannes A1 - Strehle, Jens A1 - Weiss, Franziska A1 - Wieder, Gesine A1 - Wieland, Alfred A1 - Zaiser, Judith A1 - Zimmermann, Sina A1 - Walter, Henrik A1 - Lenz, Bernd A1 - Deserno, Lorenz A1 - Smolka, Michael N. A1 - Liu, Shuyan A1 - Ebner-Priemer, Ulrich Walter A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002). Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 805 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-571460 SN - 1866-8364 IS - 805 ER - TY - JOUR A1 - Deeken, Friederike A1 - Reichert, Markus A1 - Zech, Hilmar A1 - Wenzel, Julia A1 - Wedemeyer, Friederike A1 - Aguilera, Alvaro A1 - Aslan, Acelya A1 - Bach, Patrick A1 - Bahr, Nadja Samia A1 - Ebrahimi, Claudia A1 - Fischbach, Pascale Christine A1 - Ganz, Marvin A1 - Garbusow, Maria A1 - Großkopf, Charlotte M. A1 - Heigert, Marie A1 - Hentschel, Angela A1 - Karl, Damian A1 - Pelz, Patricia A1 - Pinger, Mathieu A1 - Riemerschmid, Carlotta A1 - Rosenthal, Annika A1 - Steffen, Johannes A1 - Strehle, Jens A1 - Weiss,, Franziska A1 - Wieder, Gesine A1 - Wieland, Alfred A1 - Zaiser, Judith A1 - Zimmermann, Sina A1 - Walter, Henrik A1 - Lenz, Bernd A1 - Deserno, Lorenz A1 - Smolka, Michael N. A1 - Liu, Shuyan A1 - Ebner-Priemer, Ulrich Walter A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany JF - JAMA Network Open N2 - Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002). Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals. Y1 - 2022 U6 - https://doi.org/10.1001/jamanetworkopen.2022.24641 SN - 2574-3805 VL - 5 SP - 1 EP - 11 PB - JAMA Network / American Medical Association CY - Chicago, Illinois, USA ET - 8 ER -