Regulation of carbachol-induced c-fos mRNA expression in AR42J cells by somatostatin receptor subtypes 1, 2, and 3.
BACKGROUND
Somatostatin is an inhibitory peptide that exerts its effects tissue-specifically by activating one or more of five receptors (SSTR 1-5). Although several studies have examined which SSTR subtypes control gastrointestinal function, effects of somatostatin on pancreatic gene expression are not well defined.


OBJECTIVE
To examine the effects of somatostatin and newly synthesized selective SSTR agonists on the cholinergically stimulated expression of the immediate early response gene


RESULTS
In pancreatic acinar AR42J cells, polymerase chain reaction analysis revealed that mRNAs for SSTR 1, 2, and 3 were expressed. SSTR 4 and 5 were not detected. When AR42J cells were exposed to the cholinergic agonist carbachol in the presence of somatostatin or selective SSTR agonists, significant and dose-dependent reductions in agonist-induced levels of mRNA were noted. Pretreatment with agonists specific for SSTR 4 or 5 had no inhibitory effects. The inhibitory actions of somatostatin were pertussis toxin-sensitive. In addition, since somatostatin did not affect intracellular calcium homeostasis, the inhibitory actions of somatostatin are independent of calcium signaling.


CONCLUSIONS
The current studies demonstrate that somatostatin inhibits carbachol-induced increases in expression by interacting with somatostatin receptor subtypes 1, 2, and 3. In addition, because somatostatin did not affect intracellular calcium homeostasis, it can be concluded that SSTR actions are independent of carbachol-stimulated calcium signaling.
Cowles
Robert A
RA
Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Segura
Bradley J
BJ
Mulholland
Michael W
MW
D000818:Animals; D020013:Calcium Signaling; D002217:Carbachol / Q000037:antagonists & inhibitors*; D002460:Cell Line; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D010179:Pancreas / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017481:Receptors, Somatostatin / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology; D015533:Transcriptional Activation
D018679:Cholinergic Agonists; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C101130:somatostatin receptor type 1; D013004:Somatostatin; D002217:Carbachol; C093733:somatostatin receptor 2