The role of the C-terminal region of rat brain natriuretic peptide in receptor selectivity.
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have different C-terminal tail structures compared with the rather conservative ring structures which consist of 17 amino acid residues. To examine the different effects of the tail structures of ANP and BNP on their interaction with receptors, we synthesized several peptide analogs and measured their biological actions in three different assay systems. Deletion of the C-terminal tail from rat BNP did not effect the vasorelaxation activity against rat aorta, but it promoted cGMP production in cultured rat aortic smooth muscle cells (RASMC). Deletion of the C-terminal tail from rat ANP diminished both vasorelaxant and cGMP producing activities. In a binding competition assay with RASMC and [125I]rat ANP-(1-28), the competition activities of both ANP and BNP were greatly reduced by C-terminal deletion. In addition, we obtained agonists with novel receptor selectivity.
Shimekake
Y
Y
Shionogi Research Laboratories, Shionogi and Co., Ltd., Osaka, Japan.
Kawabata
T
T
Nakamura
M
M
Nagata
K
K
D000818:Animals; D001011:Aorta / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C058930:brain natriuretic peptide receptor; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP