V1b and CRHR1 receptor heterodimerization mediates synergistic biological actions of vasopressin and CRH.

摘要: Vasopressin (AVP) and CRH synergistically regulate adrenocorticotropin insulin release at the level of pituitary pancreas, respectively. Here, we first extended these AVP coregulation processes to adrenal medulla. We demonstrate that costimulation chromaffin cells by simultaneously induces a catecholamine secretion exceeding one induced each hormone alone, thus demonstrating net potentiation. To further elucidate molecular mechanisms underlying this synergism, coexpressed human V1b receptor (CRHR)1 in HEK293 cells. In heterologous system, also potentiated CRH-stimulated cAMP accumulation dose-dependent saturable manner. This effect was only partially mimicked phorbol ester or inhibited phospholipase C inhibitor finding suggests existence an new mechanism, independent from second messenger cross talk. Similarly, AVP-induced inositol phosphates production....