AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 2 291-G297, Copyright © 1996 by American Physiological Society

ARTICLES

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

L. Scott, V. Prpic, W. D. Capel, S. Basavappa, A. W. Mangel, T. W. Gettys and R. A. Liddle
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

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.

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