Adrenotensin: an ADM gene product with the opposite effects of ADM

The purpose of the present study was to investigate the effects of putative products of the ADM gene, other than ADM including, prodepin, proADM45-92 and proADM153-185 on cat pulmonary arterial (PA) rings with or without precontraction with U46619. Addition of proADM153-185 (3 x 10(-10)-10(-6) M) increased tension in a concentration-dependent manner in cat PA rings without precontraction. When vessels were precontracted with U46619, ADM(3 x 10(-10)-10(-6) M) produced a concentration-dependent vasorelaxant response, whereas proADM153-185 produced a weak concentration-dependent contractile response. Prodepin and proADM45-92 up to 10(-6)M had no activity on PA rings. Since proADM153-185, similar to ADM, would be expected to be released in free form following endopeptidase-induced cleavage, the present data suggest proADM undergoes proteolytic processing to release peptides with divergent vascular effects. Thus, the present data also suggest that proADM153-185 may represent a novel product of the ADM gene and term this putative new substance "adrenotensin".