Adrenomedullin suppresses mitogenesis in rat mesangial cells via cAMP pathway.

Adrenomedullin (ADM) is a vasoactive peptide that was recently localized in renal glomeruli. In the present study we explored whether ADM stimulates cAMP system in glomerular mesangial cells (MC) and whether it can via "negative-crosstalk" inhibit the mitogen-activated protein kinase (MAPK) and thus suppress proliferation of MC. We found that ADM elicited accumulation of cAMP and in situ activation of protein kinase A (PKA) in cultured MC. Addition of 1 nM ADM to incubation media inhibited the proliferation in both quiescent MC and cells maximally stimulated by PDGF and also decreased the activation of MAPK induced by PDGF. These results indicate that ADM can suppress MC mitogenesis and suggest that it may function as an endogenous paracrine supressor of MC proliferation.