Stimulation of rat pancreatic tumoral AR4-2J cell proliferation by pituitary adenylate cyclase-activating peptide.
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 less than 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 mumol/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.
Buscail
L
L
Inserm U151, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Cambillau
C
C
Seva
C
C
Scemama
J L
JL
De Neef
P
P
Robberecht
P
P
Christophe
J
J
Susini
C
C
Vaysse
N
N
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D015282:Octreotide / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D037342:Pertussis Toxin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D037361:Adenylate Cyclase Toxin; D007328:Insulin; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010566:Virulence Factors, Bordetella; D014660:Vasoactive Intestinal Peptide; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D037342:Pertussis Toxin; D009955:Ornithine Decarboxylase; D000262:Adenylyl Cyclases; D015282:Octreotide