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Human lung VIP-receptors in health and cancer
297
In v i t r o effects of secretin, vasoactive intestinal peptide (VIP) and Gila Ibnster venom on cyclic ANP levels and amylase secretion from rat pancreatic acini. J.P. D E ~ C . DAMIEN, P. POLOCZEK, J. WINAND and J. CHRISTOPHE (Dept. of Biochemistry and Nutrition, Medical School, Universit~ Libre de Bruxelles, Brussels, Belgium). By analyzing dose-effect curves on cyclic AMP levels (in the presence of 0.5 mM IBMX) and concomitant amylase secretion, we observed three classes of secretin receptors coupled to adenylate cyclase in rat pancreatic acini : high a f f i n i t y receptors (EC50 0.3 hi,l) probably related to ductal c e l i s , and intermediate (EC50 10 nM) and low a f f i n i t y (EC50 100 nI,1) receptors concerned with amylase release from acinar cells (the low a f f i n i t y receptors being reponsible for most of the exocrine secretion). VIP also bound to more than one class of receptors according to cyclic AMP elevations. Tile occupancy of high a f f i n i t y receptors (EC50 5 nM) led to modest increases in amylase release (+30 %) and cyclic AMP levels (+200 %) that were similar to those obtained with secretin acting on intermediate a f f i n i t y receptors. Gila Monster venom provoked monophasic elevations of cyclic A~IP and amylase secretion that were, respectively, 30 % lower and 3-fold higher than those attained with secretin. When used at maxima! concentration CCK-8 potentiated amylase release by secretin, VIP, and Gila ~1onster venom while inhibiting the production of cyclic AMP induced by the l a t t e r agents. The d i s t i n c t effects of I B ~ , Ro 20-1724, and theophylline on the dose-response curves of secretin, VIP, and Gila flonster venom on cyclic AMP levels implied a metabolic compartmentation of cyclic AMP. These results suggest that secretin, VlP, and Gila Monster venom increased amylase release via receptors coupled to adenylate cyclase, the efficiency of stimulus-secretion coupling depending on the type of receptors occupied and not on the total amount of cyclic AMP produced.
Human Lung VIP-Receptors
in Health and Cancer.
M. DELHAYE 1 , G. TATON 2 , P. ROBBERECHT l, J. CHRISTOPHE 1 . (ZDepartment of Biochemistry and Nutrition, Medical School, Universitd Libre de Bruxelles, Boulevard de Waterloo, 115, B - I000 Brussels, BELGIUM. 2Department of Surgery, Erasme Hospital, B - 1070 Brussels, BELGIUM). • he response of a crude particulate adenylate cyclase preparation from surgically removed normal and tumoral human lung were investigated. In normal human lung, the biphasic pattern of stimulation of the adenylate cyclase activity by VIP suggested the presence of two classes of VIP receptors coupled to the enzyme : a high affinity 5 type with equal affinity for VIP and (val) secretin and a low affinity type with affinity decreasing in the order VIP > (val 5) secretin > secretin. The stimulation of adenylate cyclase by secretin and (val 5) secretin was also biphasic, suggesting the coexistence of high and low affinity secretin receptors. Secretin - (7 - 27) was able to inhibit completely the secretin stimulation acting through high affinity secretin receptors but exerted no effect on the stimulation operating through low affinity secretin receptors and on the stimulation by VIP. This might indicate that the low affinity secretin receptors were in fact "VIP-preferring receptors". The adenylate cyclase activity was further characterized in 5 pulmonary tumors : two epidermo[d and three glandular epitheliomas. All the specimens studied possessed an adenylate cyclase stimulated by GTP, Gpp (NH) p, NaF, isoproterenol, VIP and secretin. The effect of VIP was markedly reduced in epidermo[d epitheliomas but only slightly impaired (i case) or increased (2 cases) in glandular epitheliomas. To conclude, it appears that three classes of VIP-secretin receptors coupled to adenylate cyclase can be identified in human lung membranes : two classes of VIP-preferring receptors and one class of secretin-preferring receptors. Lung epitheliom&s p o s s e s ~ VIP-receptors coupled to a membrane adenylate cyclase. It is possible that determination of hormonal stimulation of adenylate cyclase could be a valuable marker for differentiating lung tumors.
In v i t r o effects of secretin, vasoactive intestinal peptide (VIP) and Gila Ibnster venom on cyclic ANP levels and amylase secretion from rat pancreatic acini. J.P. D E ~ C . DAMIEN, P. POLOCZEK, J. WINAND and J. CHRISTOPHE (Dept. of Biochemistry and Nutrition, Medical School, Universit~ Libre de Bruxelles, Brussels, Belgium). By analyzing dose-effect curves on cyclic AMP levels (in the presence of 0.5 mM IBMX) and concomitant amylase secretion, we observed three classes of secretin receptors coupled to adenylate cyclase in rat pancreatic acini : high a f f i n i t y receptors (EC50 0.3 hi,l) probably related to ductal c e l i s , and intermediate (EC50 10 nM) and low a f f i n i t y (EC50 100 nI,1) receptors concerned with amylase release from acinar cells (the low a f f i n i t y receptors being reponsible for most of the exocrine secretion). VIP also bound to more than one class of receptors according to cyclic AMP elevations. Tile occupancy of high a f f i n i t y receptors (EC50 5 nM) led to modest increases in amylase release (+30 %) and cyclic AMP levels (+200 %) that were similar to those obtained with secretin acting on intermediate a f f i n i t y receptors. Gila Monster venom provoked monophasic elevations of cyclic A~IP and amylase secretion that were, respectively, 30 % lower and 3-fold higher than those attained with secretin. When used at maxima! concentration CCK-8 potentiated amylase release by secretin, VIP, and Gila ~1onster venom while inhibiting the production of cyclic AMP induced by the l a t t e r agents. The d i s t i n c t effects of I B ~ , Ro 20-1724, and theophylline on the dose-response curves of secretin, VIP, and Gila flonster venom on cyclic AMP levels implied a metabolic compartmentation of cyclic AMP. These results suggest that secretin, VlP, and Gila Monster venom increased amylase release via receptors coupled to adenylate cyclase, the efficiency of stimulus-secretion coupling depending on the type of receptors occupied and not on the total amount of cyclic AMP produced.
Human Lung VIP-Receptors
in Health and Cancer.
M. DELHAYE 1 , G. TATON 2 , P. ROBBERECHT l, J. CHRISTOPHE 1 . (ZDepartment of Biochemistry and Nutrition, Medical School, Universitd Libre de Bruxelles, Boulevard de Waterloo, 115, B - I000 Brussels, BELGIUM. 2Department of Surgery, Erasme Hospital, B - 1070 Brussels, BELGIUM). • he response of a crude particulate adenylate cyclase preparation from surgically removed normal and tumoral human lung were investigated. In normal human lung, the biphasic pattern of stimulation of the adenylate cyclase activity by VIP suggested the presence of two classes of VIP receptors coupled to the enzyme : a high affinity 5 type with equal affinity for VIP and (val) secretin and a low affinity type with affinity decreasing in the order VIP > (val 5) secretin > secretin. The stimulation of adenylate cyclase by secretin and (val 5) secretin was also biphasic, suggesting the coexistence of high and low affinity secretin receptors. Secretin - (7 - 27) was able to inhibit completely the secretin stimulation acting through high affinity secretin receptors but exerted no effect on the stimulation operating through low affinity secretin receptors and on the stimulation by VIP. This might indicate that the low affinity secretin receptors were in fact "VIP-preferring receptors". The adenylate cyclase activity was further characterized in 5 pulmonary tumors : two epidermo[d and three glandular epitheliomas. All the specimens studied possessed an adenylate cyclase stimulated by GTP, Gpp (NH) p, NaF, isoproterenol, VIP and secretin. The effect of VIP was markedly reduced in epidermo[d epitheliomas but only slightly impaired (i case) or increased (2 cases) in glandular epitheliomas. To conclude, it appears that three classes of VIP-secretin receptors coupled to adenylate cyclase can be identified in human lung membranes : two classes of VIP-preferring receptors and one class of secretin-preferring receptors. Lung epitheliom&s p o s s e s ~ VIP-receptors coupled to a membrane adenylate cyclase. It is possible that determination of hormonal stimulation of adenylate cyclase could be a valuable marker for differentiating lung tumors.