Attenuation of gastrin-induced gastric acid secretion by antisense oligonucleotide to the CCKB/gastrin receptor.
The effects of treatment with CCK receptor antagonists or administration of an antisense oligonucleotide to the gastrin receptor, on gastrin-I and cholecystokinin-8-induced acid secretion in mouse stomach were evaluated. Administration of gastrin-I (1 microM) or cholecystokinin-8 (30 nM) stimulated acid output at the rates of 2.6 +/- 0.27 and 1.0 +/- 0.21 microEq h-1, respectively. Gastrin-I-induced acid output was significantly blocked by pretreatment of stomachs with 3R[+]-N-[2,3-dihydro-1-methyl-2-oxo-5- phenyl-1H-1,4-benzodiazepin-3-yl]-N[3-methylphenyl[urea (L-365,260; 1 microM), but not by devazepide (L-364,718; 1 microM). Cholecystokinin-8-induced acid output, on the other hand, was sensitive to both L-365,260 (100 nM) and L-364,718 (100 nM). Administration of antisense, but not mismatch, oligonucleotide significantly reduced gastrin-induced acid output, while antisense oligonucleotide treatment had no effect on cholecystokinin-8-induced acid output. These results of antagonist and antisense oligonucleotide studies suggest that gastrin-I and cholecystokinin-8 may involve different receptor subtypes in stimulating gastric acid secretion in mice, and that antisense oligonucleotide administration may serve an useful tool in characterizing CCK/gastrin receptor subtypes.
Rao
R K
RK
Department of Pediatrics, Medical University of South Carolina, Charleston 29407, USA.
Lopez
Y
Y
Lai
J
J
Riviere
P J
PJ
Junien
J L
JL
Porreca
F
F
D000818:Animals; D001483:Base Sequence; D001570:Benzodiazepinones / Q000494:pharmacology; D020109:Devazepide; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010671:Phenylurea Compounds; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D012844:Sincalide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects
D001570:Benzodiazepinones; D005755:Gastrins; D006727:Hormone Antagonists; D016376:Oligonucleotides, Antisense; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; C036227:gastrin I; D020109:Devazepide; D012844:Sincalide