Effects of histamine H1 receptor signaling on glucocor6coid receptor ac6vity. Role of canonical and non-canonical pathways.

ZAPPIA DANIEL; GRANJA GALEANO GINA; FERNADEZ NATALIA; SHAYO CARINA; DAVIO CARLOS; FITZSIMONS CARLOS; MONCZOR FEDERICO

LEIDEN

Congreso; Nuclear Receptor Research Network Meeting‏; 2015

Nuclear Receptor Research Network

1. Ac6va6on of the H1R triggers a dual regulatory mechanism on GRac6vity, involving both G-protein Gαq and Gβγ subunits.2. Whereas Gαq has an inhibitory effect via a PLC-mediatedpathway, Gβγs enhance GR ac6vity via JNK.3. When agonists bind to and ac6vate the H1R, Gαq and Gβγ aresimultaneously released. Under these circumstances, the Gβγpathway prevails, resul6ng in an overall H1R-mediatedpoten6a6on of GR ac6vity.4. When an6histamines bind to, and inac6vate the H1R, apoten6a6ng effect on GR ac6vity is observed too, which can beapributed to the inac6va6on of the Gαq-PLC-inhibitory pathway.5. Histamine and an6histamines were able to poten6ate Dexinducedtranscrip6onal ac6vity (transac6va6on andtransrepression).6. Our results suggest that H1R ac6va6on may be able to poten6atethe transcrip6onal ac6vity induced by GR synthe6c and naturalagonists.7. (For further reading this paper accepted in Sci. Reports, as perNovember 2015.)