Activation of the cAMP-generating system by vasoactive intestinal polypeptide (VIP) in the human laryngeal malignant cell line HEp-2.
In the presence of 3-isobutyl-l-methylxanthine, VIP produced a dose-related (3 X 10(-9)-10(-7) M) increase (8-fold) in cAMP production in isolated HEp-2 cells incubated at 15 degrees C in KRP buffer. Among the peptides structurally related to VIP, including secretin (10(-7) M), pancreatic glucagon (10(-6) M), PHI, somatostatin-14 (10(-6) M), hpGRF (10(-8)-4 X 10(-6) M), GIP (2 X 10(-7) M), only PHI (3 X 10(-7) M and above) is able to activate the cAMP-generating system in HEp-2 cells, but at 10(2) times lower potency. Under the same conditions, histamine (10(-3) M) was also ineffective, while PGE2 (10(-7)-10(-4) M) increased (4-fold) basal cAMP levels in HEp-2 cells. The VIP effect is related to the interaction of the peptide on VIP recognition sites (125I-VIP-binding capacity), coupled to the membrane-bound adenylate cyclase. The results indicate that the transformed laryngeal cell line HEp-2 possesses a receptor-cAMP system preferentially activated by VIP (relative potencies: VIP greater than PHI much greater than other peptides of the secretin family), and suggest that this neuropeptide could modulate biological functions in normal laryngeal epithelia in man.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism*; D010451:Peptide PHI; D010455:Peptides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D010451:Peptide PHI; D010455:Peptides; D011956:Receptors, Cell Surface; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine