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Activation of the cAMP-generating system by vasoactive intestinal polypeptide (VIP) in the human laryngeal malignant cell line HEp-2
Authors:Annie Prost  Shahin Emami  Gabriel Rosselin  Christian Gespach
Institution:(1) INSERM U. 55, Hôpital St. Antoine, 184 rue du Fg. St. Antoine, 75571 Paris Cedex 12, France;(2) Service central d'Hématologie (Laboratoire d'Immunologi), Hôpital Tenon, 4 rue de la Chine, 75970 Paris Cedex 20, France
Abstract:In the presence of 3-isobutyi-l-methylxanthine, VIP produced a dose-related (3×10–9–10–7 M) increase (g-fold) in cAMP production in isolated HEp-2 cells incubated at 15°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 (10–8–4×10–M), GIP (2×10–7 M), only PHI (3×10–7 M and above) is able to activate the cAMP-generating system in HEp-2 cells, but at 102 times lower potency. Under the same conditions, histamine (10–3 M) was also ineffective, while PGE 2 (10–7–10–4 M) increased (0-fold) basal cAMP levels in HEp-2 cells. The VIP effect is related to the interaction os the peptide on VIP recognition sites (12SI-VIP-binding capacity ), coupled to the membrane-bound adenylate cyclase . The results indicate that the transformed laryngeal cell line HEp-2 possessesa receptor-cAMP system preferentially activated by VIP (relative potencies: VIP > PHI Gt other peptides of the secretin family), and suggest that this neuropeptide could modulate biological functions in normal laryngeal epithelia in man.
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