In HGT-1 cells incubated at 20 degrees C for 15 min with 1 mM
3-isobutyl-1-methylxanthine (
IBMX),
histamine (10(-4)M) increased basal cAMP levels from 2.12 +/- 0.14 to 22.9 +/- 2 pmol per 10(6) cells, with a potency of 6.4 X 10(-6)M.
IBMX was added in order to inhibit cAMP degradation by low and high Km cAMP-
phosphodiesterases (cAMP-PDE). The use of specific H1,
H2 agonists or antagonists indicated that the
histamine effect was due to an interaction with typical
H2 -receptors that are involved in gastric acid secretion.
Cyclic AMP levels were also increased (10-fold) by
vasoactive intestinal peptide VIP (3 X 10(-11) - 10(-8)M). Porcine
peptide having N-terminal
histidine and C-terminal
isoleucine amide (PHI) and
secretin were respectively 80 and 3600 times less potent than VIP and did not produce additive effect when tested in combinations with VIP. This observation indicates that these two
peptides, structurally related to VIP, are acting through the recognition sites for VIP. Combination of VIP and
histamine results in additive stimulation on intact cells as well as on membrane-bound
adenylate cyclase, suggesting the existence of two cell populations bearing respectively the two sets of receptors. Two other human
cancer cell lines originating from nongastric
tumors (HT-29 and HL-60) possess only VIP or
histamine receptors, respectively, indicating the gastric cellular originality of the HGT-1 cells. It is concluded that HGT-1 cells possess both VIP and
histamine H2 receptors with similar pharmacological properties to those characterized in normal human fundic glands (1,2). Therefore, this cell line can be a good model to study drugs used therapeutically during the treatment of patients for
gastric ulcer or
cancer.