Somatostatin inhibition of gastrin gene expression: involvement of pertussis toxin-sensitive and -insensitive pathways.
These studies were performed to determine the intracellular pathways involved in regulating gastrin gene expression. The inclusion of 10(-4) M forskolin or 10(-4) M dibutyryl cyclic AMP (DBcAMP) in incubation medium containing dog antral mucosa resulted in 249% and 323% increases, respectively, in gastrin mRNA levels. The stimulatory effects of forskolin and DBcAMP were both inhibited significantly by 10(-6) M somatostatin. Preincubation of antral mucosa with pertussis toxin nearly abolished the inhibitory effects of somatostatin on gastrin mRNA stimulated by forskolin, but had no effect following DBcAMP. To examine whether calcium-dependent pathways might be involved in regulating gastrin gene expression, antral mucosa was incubated with increasing concentrations of calcium or the ionophore ionomycin. Both agents produced only modest increases in gastrin mRNA, which were abolished by the addition of somatostatin to the incubation medium. These studies indicate that somatostatin appears to inhibit gastrin gene expression through mechanisms involving both pertussis toxin-sensitive and -insensitive pathways.
Harvard Digestive Diseases Center, Beth Israel Hospital, Boston, MA.
P S
PS
Karnik
H
H
Dushkin
M M
MM
Wolfe
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D015759:Ionomycin / Q000494:pharmacology; D009693:Nucleic Acid Hybridization; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D005755:Gastrins; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D013004:Somatostatin; D015759:Ionomycin; D003994:Bucladesine; D037342:Pertussis Toxin; D002118:Calcium