“…[95][96][97] This trafficking forms the basis for GPER-1 desensitization (through endocytosis), resensitization (through recycling to plasma membrane), and down-regulation (through proteolytic degradation). 98,99 On interaction with its ligand(s), GPER-1 undergoes conformational changes that result in the dissociation of Gα from Gβγ subunit, leading to the intracellular activation of phosphoinositide-3-kinase, with ensuing increase of cAMP and intracellular Ca 2+ . 95,100 The latter increases mitochondrial Ca 2+ , resulting in Ca 2+ -dependent mitochondrial cAMP production and enhanced aldosterone secretion.…”