Protein kinase C activation inhibits receptor-evoked inositol trisphosphate formation and induction of cytosolic calcium oscillations by decreasing the affinity-state of the cholecystokinin receptor in pancreatic acinar cells

Autor: R.L.L. Smeets, Peter H.G.M. Willems, R.R. Bosch, J.J.H.H.M. De Pont, M. G. H. Van Mackelenbergh, K.M. Garner
Rok vydání: 1995
Předmět:
Agonist
Periodicity
medicine.medical_specialty
Physiology
medicine.drug_class
Population
Inositol 1
4
5-Trisphosphate
Inhibitory postsynaptic potential
digestive system
Cholecystokinin receptor
Sincalide
Mechanism and function of oscillating second messenger systems
chemistry.chemical_compound
Cytosol
Internal medicine
medicine
Animals
Protein kinase A
Receptor
education
Pancreas
Molecular Biology
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)
Protein Kinase C
Cholecystokinin
education.field_of_study
Dose-Response Relationship
Drug
Chemistry
Signal Processing
Computer-Assisted
Inositol trisphosphate
Cell Biology
Mechanisme en functie van oscillerende second messenger systemen
Endocrinology
Tetradecanoylphorbol Acetate
Calcium
Receptors
Cholecystokinin
Rabbits
Signal Transduction
Zdroj: Cell Calcium, 18, 471-483
Cell Calcium, 18, 6, pp. 471-483
Cell Calcium, 18, pp. 471-483
ISSN: 0143-4160
Popis: Digital-imaging microscopy of Fura-2-loaded pancreatic acinar cells revealed that the C-terminal octapeptide of cholecystokinin (CCK 8 ) dose-dependently recruited 94% of freshly isolated acinar cells in terms of receptor-evoked Ca 2+ mobilization. Maximal and half-maximal cell-recruitment were reached with 0.1 nM and 16.8 pM CCK 8 , respectively. The upstroke of the dose-recruitment curve consisted of cells displaying oscillatory changes in free cytosolic Ca 2+ concentration ([Ca 2+ ] i ). After having reached its maximum, the percentage oscillating cells dose-dependently decreased upon further increasing of the CCK 8 concentration. Pretreatment of the acinar cells with 0.1 μM TPA caused a rightward shift of the dose-recruitment curve but did not change the maximal effect of CCK 8 on the recruitment of oscillating cells. Half-maximal recruitment was obtained with 287 pM CCK 8 . This observation demonstrates that high levels of protein kinase C activation do not inhibit Ca 2+ oscillations at a level downstream to receptor activation. Moreover, this observation demonstrates that protein kinase C-mediated inhibition of Ca 2+ oscillations evoked by submaximal CCK 8 concentrations occurs at the receptor level, converting it from a high-affinity state into a low-affinity state. This conclusion is supported by the observation that TPA completely inhibited the recruitment of acinar cells in response to the high-affinity receptor agonist JMV-180. The inhibitory action of TPA on CCK 8 -evoked cell-recruitment was paralleled by an inhibitory effect of the phorbol ester on the CCK 8 -evoked peak increase in average inositol trisphosphate concentration in a population of acinar cells. This observation indicates that low concentrations of CCK8 interact with the high-affinity CCK receptor to increase [Ca 2+ ] i through the intermediation of inositol trisphosphate.
Databáze: OpenAIRE
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