Depolarization-stimulated cholecystokinin secretion is mediated by L-type calcium channels in STC-1 cells.
To examine the role of calcium channels in depolarization-activated cholecystokinin (CCK) release, studies were performed in an intestinal CCK-secreting cell line, STC-1. Blockade of potassium channels with barium chloride (5 mM) increased the release of CCK by 374.6 +/- 46.6% of control levels. Barium-induced secretion was inhibited by the L-type calcium-channel blocker, nicardipine. Nicardipine (10(-9)-10(-5) M) produced a dose-dependent inhibition in barium-stimulated secretion with a half-maximal inhibition (IC50) value of 0.1 microM. A second L-type calcium-channel blocker, diltiazem (10(-9)-10(-4) M), also inhibited barium-induced CCK secretion with an IC50 value of 5.1 microM. By contrast, the T-type calcium-channel blocker, nickel chloride (10(-7)-10(-8) M), failed to significantly inhibit barium-induced CCK secretion. To further evaluate a role for L-type calcium channels in the secretion of CCK, the effects of the L-type calcium channel opener, BAY K 8644, were examined. BAY K 8644 (10(-8)-10(-4) M) produced a dose-dependent stimulation in CCK release with a mean effective concentration value of 0.2 microM. Recordings of single-channel currents from inside-out membrane patches showed activation of calcium channels by BAY K 8644 (1 microM), with a primary channel conductance of 26.0 +/- 1.2 pS. It is concluded that inhibition of potassium channel activity depolarizes the plasma membrane, thereby activating L-type, but not T-type, calcium channels. The corresponding influx of calcium serves to trigger secretion of CCK.
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- Tumor Cells, Cultured
- Mice
- Electrophysiology
- Cholecystokinin
- Cardiovascular System & Hematology
- Calcium Channels
- Calcium Channel Blockers
- Calcium Channel Agonists
- Animals
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Mice
- Electrophysiology
- Cholecystokinin
- Cardiovascular System & Hematology
- Calcium Channels
- Calcium Channel Blockers
- Calcium Channel Agonists
- Animals
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester