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Adrenomedullin stimulates DNA synthesis and cell proliferation via elevation of cAMP in Swiss 3T3 cells
Author(s) -
Withers Dominic J.,
Coppock Hedley A.,
Seufferlein Thomas,
Smith David M.,
Bloom Stephen R.,
Rozengurt Enrique
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01427-6
Subject(s) - adrenomedullin , intracellular , dna synthesis , 3t3 cells , transfection , cell growth , microbiology and biotechnology , phosphorylation , cell culture , biology , receptor , chemistry , endocrinology , medicine , biochemistry , dna , genetics
Our results demonstrate that the novel vasoactive regulatory peptide adrenomedullin is a potent mitogen for Swiss 3T3 cells. Acting via a specific adrenomedullin receptor, it stimulates a dose‐dependent increase in DNA synthesis in synergy with insulin. Additionally, adrenomedullin stimulates further progression through the cell cycle resulting in cell proliferation, an effect that was further enhanced by the presence of insulin. Adrenomedullin rapidly induces accumulation of intracellular CAMP but does not stimulate an increase in intracellular Ca 2+ , activation of protein kinase C, or tyrosine phosphorylation of intracellular substrates. Adrenomedullin‐stimulated mitogenesis is markedly enhanced in Swiss 3T3 cells stably transfected with a constitutively activated Gsα, which are highly sensitive to agents that elevate cAMP, and is inhibited by the PKA inhibitor H‐89. Adrenomedullin is, thus, identified as a novel mitogenic regulatory peptide acting via cAMP.