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pubmed:abstractText |
A non-hydrolysable guanosine nucleotide analog, GTP[S] at 200 microM, stimulated amylase secretion which was inhibited by an anti-phospholipase A2 (PLA2) antibody in permeabilized pancreatic acini, indicating that the PLA2 pathway is linked to the GTP binding protein. A high affinity cholecystokinin (CCK) receptor agonist, CCK-OPE (10 microM), and a low affinity receptor agonist, CCK-8 (0.1 microM), both caused amylase secretion in permeabilized cells. The action of CCK-OPE was abolished by the G beta antibody but not by the G alpha-q,11 antibody, whereas the opposite was true of the CCK-8 response. Biscoclaurine alkaloid isotetrandrine (10 microM), a specific inhibitor of PLA2-coupled G proteins, abolished Ca2+ oscillations and amylase secretion induced by CCK-OPE (0.1-100 nM), but not by CCK-8 (10 pM) in intact acini. Gp antagonist-2A (10 microM), which inhibits the activation of Gq, also inhibited the actions of CCK-OPE (10 pM-1 microM) in intact acini. These observations indicate that the functional unit of the heterotrimeric G protein coupled to the high affinity CCK receptor appears to be different from that linked to the low affinity CCK receptor/Gq-alpha pathway. The regulatory site of this G protein coupled to the high affinity CCK receptor is on the beta subunit of Gq protein which elicits Ca2+ oscillations and monophasic amylase secretion via the PLA2 pathway.
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