Proadrenomedullin N-terminal 20 peptide (PAMP) enhances proliferation of rat zona glomerulosa cells by activating MAPK cascade.
The effect of proadrenomedullin N-terminal 20 peptide (PAMP) on the proliferative activity of rat zona glomerulosa (ZG) cells has been investigated. Dispersed rat ZG cells were cultured in vitro for 24 h and then exposed to PAMP for an additional 24 h, and the proliferation rate was assessed by the 5-bromo-2'-deoxyuridine (BrdU) incorporation technique. PAMP dose-dependently increased the percentage of BrdU-positive cells, with a maximal effective concentration observed at 10(-8) M. The tyrosine kinase (TK) inhibitor, tyrphostin-23, and the p42/p44 MAPK inhibitor, PD-98059, abolished the proliferogenic effect of PAMP, while the protein kinase (PK) A inhibitor, H-89, and the PKC inhibitor, calphostin-C, were ineffective in blocking the response to PAMP. PAMP (10(-8) M) enhanced TK and MAPK activity of dispersed rat ZG cells. The stimulatory action of PAMP on TK activity was annulled by tyrphostin-23, while that on MAPK activity was abolished by either tyrphostin-23 or PD-98059. Taken together, these data indicate that PAMP enhances proliferation of cultured rat ZG cells, through the TK-dependent activation of p42/p44 MAPK cascade.
Rebuffat
P
P
Department of Human Anatomy and Physiology (Section of Anatomy), University of Padua, I-35121, Padua, Italy.
Gottardo
L
L
Malendowicz
L K
LK
Neri
G
G
Nussdorfer
G G
GG
D053607:Adrenomedullin; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D053607:Adrenomedullin; D020928:Mitogen-Activated Protein Kinases