Low-affinity CCK-1 receptors inhibit bombesin-stimulated secretion in rat pancreatic acini--implication of the actin cytoskeleton.
OBJECTIVE
Stimulation of low-affinity CCK-1 receptors on pancreatic acini leads to inhibition of enzyme secretion. We studied signal transduction mechanisms to identify potential causes for the reduced secretion.


RESULTS
Co-stimulation experiments with CCK, CCK-JMV-180, and bombesin revealed an inhibition of bombesin-stimulated enzyme secretion by low-affinity CCK-1 receptors. Binding of 125I-gastrin-releasing peptide (the mammalian analogue of bombesin) to acini after CCK preincubation was not altered. After a short preincubation of acini with high concentrations of CCK, intracellular calcium remained responsive to bombesin. In contrast to bombesin or CCK at concentrations of 10(-10) M or lower, high concentrations of CCK caused a strong activation of p125 focal adhesion kinase (p125(FAK)) and a marked reorganisation of the actin cytoskeleton.


CONCLUSIONS
Inhibitory mechanisms triggered by low-affinity CCK-1 receptors interrupt enzyme secretion from pancreatic acini at late stages in the signal transduction cascades since bombesin receptor binding and early signalling events remained intact after CCK preincubation. A reorganisation of the actin cytoskeleton is suggested to be the mechanism by which low-affinity CCK-1 receptors actively interrupt enzyme secretion stimulated by other receptors.
Kiehne
Karlheinz
K
I. Medizinische Universitätsklinik, Christian-Albrechts Universität Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany. kkiehne@1med.uni-kiel.de
Herzig
Karl Heinz
KH
Otte
Jan M
JM
Fölsch
Ulrich R
UR
D000199:Actins / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D046508:Culture Techniques; D003599:Cytoskeleton / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019886:Gastrin-Releasing Peptide / Q000378:metabolism / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
D000199:Actins; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C058451:JMV 180; D014443:Tyrosine; D019886:Gastrin-Releasing Peptide; D002766:Cholecystokinin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D000681:Amylases; D012844:Sincalide; D001839:Bombesin; D002118:Calcium