Search for novel peptides to increase rat platelet cAMP.

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Using the assay system which monitor the activity to increase rat platelet cAMP,we have discovered a novel hypotensive peptide, designated "adrenomedullin", in human pheochromocytoma extract. It has potent and long-lasting vasodilator effects in several vascular systems. In addition to adrenomedullin, another hypotensive peptide, termed "proadrenomedullin N-terminal 20 peptide" (PAMP) is found to be processed from the adrenomedullin precursor. Although initially isolated from human pheochromocytoma tissue and porcine adrenal medullae, adrenomedullin mRNA is highly expressed in several peripheral organs including cardiovascular tissues. Taken together with a significant increase in plasma immunoreactive adrenomedullin levels in patients with cardiovascular diseases, adrenomedullin is a novel factor regulating blood pressure and circulation. Futhermore, ubiquitous expression of adrenomedullin mRNA indicates its various biological functions as well as the existence of a novel circulation control system.