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.
Sakata
J
J
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Shimokubo
T
T
Kitamura
K
K
Nakamura
S
S
Kangawa
K
K
Matsuo
H
H
Eto
T
T
D000311:Adrenal Glands / Q000378:metabolism*; D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000494:pharmacology; D001483:Base Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000097:blood; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology; D011061:Poly A / Q000302:isolation & purification / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid
D000959:Antihypertensive Agents; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D053607:Adrenomedullin; D011061:Poly A; D012313:RNA; D004247:DNA; D000242:Cyclic AMP