Molecular cloning and biological activities of rat adrenomedullin, a hypotensive peptide.

Adrenomedullin is a new hypotensive peptide recently identified in human pheochromocytoma arising from adrenal medulla. We report here the cDNA encoding a rat adrenomedullin precursor. The precursor is 185 amino acids in length, including a 21 residue putative signal peptide at the N-terminus. Rat adrenomedullin consists of 50 amino acids similar to, but distinct from human adrenomedullin; 2 residues were deleted and 6 residues were substituted compared to those in the human peptide. In the proadrenomedullin N-terminal 20 peptide, whose amino acid sequence is present in adrenomedullin precursor, 3 amino acids were substituted. RNA blot analysis showed that rat adrenomedullin mRNA was expressed in adrenal glands, lung, kidney, heart, spleen, duodenum and submandibular glands. Synthetic rat adrenomedullin elicits a potent and long-lasting hypotensive activity in anesthetized rats.