Adenylate cyclase activity in human pancreatic adenocarcinoma cell lines.
CONCLUSIONS
BxPC-3, Hs 766T, Capan-2, Panc-1, and Capan-1 cells possess receptors for VIP and beta-adrenergic agonists that are functionally coupled to adenylate cyclase. In this respect, they resemble pancreatic duct cells. However, we speculate that the process of neoplastic transformation has either downregulated the expression of secretin receptors or led to a defect in the receptor itself, placing a question mark over the usefulness of these adenocarcinoma cell lines as models of the pancreatic ductal epithelium


BACKGROUND
Because of the importance of ducts in pancreatic disease, we wished to establish which duct cells receptors are functional on adenocarcinoma cell lines.


METHODS
We investigated the expression of agonist-stimulated adenylate cyclase activity in six human pancreatic adenocarcinoma cell lines. Known stimulants of pancreatic ductal secretion, VIP, PHI, secretin, beta-adrenergic, and dopamine, were tested.


RESULTS
For responsive cell lines, VIP was the most effective stimulant followed by adrenaline, isoprenaline, PHI, and secretin. Dopamine was without effect. Since high concentrations of PHI and secretin were required to stimulate cyclase activity, their effect is probably mediated by VIP receptors. Based on the degree of stimulation observed with the individual agonist, Hs 766T and BxPC-3 were the most responsive cell lines, followed by Capan-2 and Capan-1, and finally Panc-1. MIAPaCa-2 cells did not respond to any of the agonists tested.
al-Nakkash
L
L
Department of Physiological Sciences, University Medical School, Newcastle upon Tyne, UK.
Simmons
N L
NL
Lingard
J M
JM
Argent
B E
BE
D000230:Adenocarcinoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D006801:Humans; D009479:Neuropeptides / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D001639:Bicarbonates; D009479:Neuropeptides; D011956:Receptors, Cell Surface; D005576:Colforsin; D000262:Adenylyl Cyclases; D004298:Dopamine