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Stimulation of rat pancreatic tumoral AR4-2J cell proliferation by Pituitary Adenylate cyclase-activating peptide

par Buscail, Louis ;Cambillau, Chantal;Seva, Catherine;Scemama, Jean Luc;Neef, Philippe De;Robberecht, Patrick ;Christophe, Jean ;Susini, Christiane;Vaysse, Nicole
Référence Gastroenterology, 103, 3, page (1002-1008)
Publication Publié, 1992

Article révisé par les pairs

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Résumé :

In the present work the effects of the novel neuropeptide Pituitary Adenylate Cyclase Activating Peptide (PACAP) on both AR4-2J cell growth and the modulation of ornithine decarboxylase activity were investigated. Both PACAP38 and the amidated form PACAP27 caused a concentration-dependent stimulation of AR4-2J cell growth; the maximal increase was seen at 1 nmol/L (30% above control, P < 0.01) with a half-maximal effect at 0.01 nmol/L. Ornithine decarboxylase activity was also increased by PACAP in a dose-dependent manner, reaching half-maximal stimulation at 0.5 nmol/L. The addition of 1 nmol/L of somatostatin analog SMS 201-995 totally suppressed PACAP-stimulated AR4-2J cell growth. Vasoactive intestinal polypeptide (3 μmol/L) and 8-bromo-cyclic adenosine monophosphate (1 mmol/L) had no effect on cell proliferation. Treatment of cells by pertussis toxin (25 ng · mL-1 · day-1) suppressed PACAP-stimulated AR4-2J cell growth but enhanced PACAP-induced stimulation of adenylate cyclase activity. It was concluded that PACAP stimulates AR4-2J cell proliferation by a mechanism that seems independent of cyclic adenosine monophosphate production. The mitogenic effect of PACAP depends on a pertussis toxin-sensitive G protein and is associated with an increase of ornithine decarboxylase activity. © 1992.