Andrea Hembre Ulsund has looked into the interaction between G protein-coupled receptors and serotonin receptors, as well as intracellular cAMP signaling elicited by 5-HT4 serotonin receptors in normal and failing hearts.
MAIN RESULTS:
THESIS DEFENCE:
Thesis: G protein coupling and signaling of Gs-coupled serotonin receptors
Candidate: Andrea Hembre Ulsund
Time: September 10, 2019 at 13:15
Place: University of Oslo, Domus Odontologica: Store auditorium
Link to university website
SUMMARY:
(3) Stimulation of the 5-HT4 serotonin receptor in failing hearts induces a positive inotrophic effect. This happens through cAMP messaging. 5-HT4 appears to be more efficiently coupled to contractility than β adrenergic receptors, as cAMP increase is lower but contractility the same. Further research showed that 5-HT4-dependent cAMP increase was compartmented close to the contractile apparatus of the cell, in near proximity of troponin I. Phosphodiesterase 4 appears downregulated in heart failure, increasing the contribution of phospodiesterase 3 on cAMP activation.
(1/2) The 5-HT7 serotonin receptor and the G-proteins coupled to it are associated even in the absence of ligand, as opposed to the 5-HT4 and β adrenergic receptors. Agonist activation of 5-HT7 leads to conformational change of the Gα subunit and a slow dissociation of the Gγ subunit from both the receptor and Gα. Ulsund’s research finds that the same domains responsible for this preassociation are involved in low potency activation of adenylyl cyclase.
REFERENCES:
(1) Andressen, K. W., Ulsund, A. H., Krobert, K. A., Lohse, M. J., Bünemann, M., & Levy, F. O. (2017). Related GPCRs couple differently to Gs: preassociation between G protein and 5-HT7 serotonin receptor reveals movement of Gαs upon receptor activation. The FASEB Journal, 32(2), 1059-1069.
(2) Ulsund, A. H., Dahl, M., Frimurer, T. M., Manfra, O., Schwartz, T. W., Levy, F. O., & Andressen, K. W. (2018). Preassociation between the 5-HT7 serotonin receptor and G protein Gs: molecular determinants and association with low potency activation of adenylyl cyclase. The FASEB Journal, 33(3), 3870-3886.
Priority at NORHEART events
Opportunities for travel and exchange grants
E-mail updates on key NORHEART events
23 students completed NORHEART’s Introductory Course to Cardiovascular Research and Medicine in Oslo 17–21 October. As usual,…
The 20th Annual Norwegian Symposium on Heart Research was arranged by NORHEART and the Department…
The Norwegian Health Association has awarded the prestigious 2022 Heart Research Award (Hjerteforskningsprisen) to professor Eva…
NORHEART was established in 2013 as part of the research school program of the Research…