Regulation of intestinal cholecystokinin and somatostatin mRNA by bombesin in rats.
The neuropeptide bombesin has been shown to stimulate secretion of several gastrointestinal hormones, including cholecystokinin (CCK). We have previously demonstrated that stimulation of CCK release by feeding is associated with an increase in steady-state intestinal CCK mRNA levels. The purpose of the present study was to determine whether bombesin stimulates CCK release in rats and, if so, to determine whether bombesin regulates CCK mRNA levels in a manner similar to that of feeding. To establish a proper dose of bombesin for stimulating CCK release, rats received 1-h intravenous infusions of 0.25, 1, 4, or 16 micrograms.kg-1.h-1 bombesin. Basal plasma CCK levels averaged 1.8 +/- 0.4 pM and increased to peak levels of 2.9 +/- 0.6 pM within 15 min of infusion with 4 micrograms.kg-1.h-1 bombesin (the maximally effective dose). With the use of this dose, rats then received infusions of bombesin or saline lasting up to 24 h. At 1, 2, 4, and 24 h, animals were killed for collection of plasma for CCK measurements and of intestine for measurements of intestinal CCK and somatostatin mRNA levels. Bombesin treatment stimulated an increase in plasma CCK levels at 1 h, but levels declined to basal by 4 h, where they remained at 24 h. Despite increasing plasma CCK levels, bombesin infusion, unlike dietary stimulation, had no effect on duodenal CCK mRNA levels. Finally, to determine whether the decrease in plasma CCK levels after prolonged bombesin treatment was due to tachyphylaxis, rats treated with bombesin for 4 h were also fed soybean trypsin inhibitor (a known stimulus of CCK secretion).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
S
S
Kanayama
R A
RA
Liddle
D000199:Actins / Q000235:genetics; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology*; D002766:Cholecystokinin / Q000097:blood* / Q000378:metabolism; D004750:Enteral Nutrition; D005755:Gastrins / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007700:Kinetics; D008297:Male; D010671:Phenylurea Compounds; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C058121:L 365260; D013004:Somatostatin; D002766:Cholecystokinin; D001839:Bombesin