Transient agonist-induced regulation of the cholecystokinin-A and cholecystokinin-B receptor mRNA levels in rat pancreatic acinar AR42J cells.
BACKGROUND
CCK-8 and gastrin exert multiple effects in the gastrointestinal tract and the nervous system. Their actions are mediated via the G-protein coupled CCK-A and CCK-B receptors.


METHODS
Rat pancreatic acinar tumor AR42J cells express both CCK receptor subtypes. This cell line was used to characterize the agonist-dependent regulation of CCK-A and CCK-B receptor gene expression.


RESULTS
CCK-8 (10 nM) or gastrin (10 nM) reduced CCK-A receptor mRNA expression to 56% and 53%, respectively 2 h after hormonal exposure. In contrast, the level of CCK-B receptor gene expression was upregulated to 157% and 153%, respectively. These effects are most probably linked to the CCK-B receptor in AR42J cells. The phorbolester PMA (100 nM), a protein kinase C activator, downregulated CCK-A receptor expression but did not affect CCK-B receptor gene transcription. Activation of protein kinase A by forskolin (10 microM) or Bt(2)cAMP (100 microM) is not involved in the transient regulation of CCK receptor mRNA expression. Both elevated CCK-B and decreased CCK-A receptor mRNA expression returned to basal levels 6 h after continuous stimulation.


CONCLUSIONS
These results demonstrate that CCK-A and CCK-B receptor mRNA levels are differentially regulated by their agonists via distinct signal transduction mechanisms in AR42J cells.
Günther
Rainer
R
Laboratory of Molecular Gastroenterology, 1st Department of Medicine, Christian-Albrechts-University of Kiel, Germany. rguenther@1med.uni-kiel.de
Carstens
Ove C
OC
Schmidt
Wolfgang E
WE
Fölsch
Ulrich R
UR
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D005755:Gastrins / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics*; D012844:Sincalide / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D003609:Dactinomycin; D005576:Colforsin; C058121:L 365260; D003994:Bucladesine; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate