Beta-adrenergic regulation of cholecystokinin secretion in STC-1 cells.

Published

Journal Article

Previously, it has been shown that an increase in adenosine 3',5'-cyclic monophosphate (cAMP) levels stimulates intestinal secretion of cholecystokinin (CCK); however, the mechanisms for increasing intracellular cAMP levels are not known. Using the CCK-secreting intestinal cell line, STC-1, we evaluated whether beta-adrenergic receptors (beta-ARs) might be present on STC-1 cells and whether they stimulated CCK release through increases in cAMP. Photoaffinity labeling of beta-ARs from solubilized STC-1 cell membranes revealed photoincorporation of the agonist [125I]iodocyanopindolol into an approximately 75-kDa band. Addition of the beta-AR agonist, isoproterenol, in the presence of 3-isobutyl-1-methylxanthine, produced a concentration-dependent increase in both cAMP levels and CCK release. Blockade of beta 1- and/or beta 2-ARs significantly inhibited isoproterenol-stimulated increases in cAMP production and CCK release. With the use of fura 2-loaded cells to measure changes in intracellular Ca2+ concentration ([Ca2+]i), isoproterenol stimulation was found to increase cytosolic Ca2+ levels. To evaluate whether this increase in [Ca2+]i was due to release of Ca2+ or influx of Ca2+, cells were treated with the L-type calcium channel blocker, diltiazem, which inhibited isoproterenol-stimulated CCK secretion. Furthermore, in patch-clamp studies with inside-out membrane patches, addition of the catalytic subunit of protein kinase A activated diltiazem-sensitive Ca2+ channels. It is concluded that beta-ARs are present on STC-1 cells and are coupled to the production of cAMP, which may increase CCK release through a calcium-dependent process.

Full Text

Duke Authors

Cited Authors

  • Scott, L; Prpic, V; Capel, WD; Basavappa, S; Mangel, AW; Gettys, TW; Liddle, RA

Published Date

  • February 1996

Published In

Volume / Issue

  • 270 / 2 Pt 1

Start / End Page

  • G291 - G297

PubMed ID

  • 8779971

Pubmed Central ID

  • 8779971

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajpgi.1996.270.2.G291

Language

  • eng

Conference Location

  • United States