Brain-gut peptides and the control of food intake.
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Biomedical subjects
Publications and source records attributed to J Gibbs.
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The satiety effect of intraperitoneal injections of the synthetic tetradecapeptide bombesin (BBS) was examined in rats equipped with chronic gastric cannulas. BBS produced potent, dose-related suppressions of both sham feeding (on days when gastric cannulas were open) and feeding (on days when gastric cannulas were closed). BBS not only suppressed sham feeding, but also elicited the behavioral sequence characteristic of normal satiety. The results demonstrate the potency of BBS in eliciting behavioral satiety under conditions in which gastric, intestinal and postabsorptive mechanisms are minimally activated by ingested food. These findings are consistent with previous reports suggesting a role for BBS in satiety.
Rhesus monkeys prepared with chronic cannulae implanted in the stomach and duodenum were water deprived for 22.5 hr. With both cannulae closed, a mean of 137 ml was drunk within a 60-min period. When ingested water drained freely from an open gastric cannula, continuous drinking far in excess (878 ml mean intake) of normal occurred. Sham drinking also exceeded (634 ml mean intake) normal when ingested water drained through an open duodenal cannula. This pattern of continuous sham drinking indicates that oropharyngeal stimulation is not sufficient alone, or together with the passage of water through the stomach and the initial part of the duodenum, to terminate drinking. Duodenal infusions of water (25-100 ml) slowed or stopped gastric sham drinking in a dose-dependent fashion, but equivalent infusions of isotonic saline were without effect. Thus, pre- or postabsorptive signals at or beyond the level of the intestine distal to the site of the duodenal cannula are probably important for the termination of drinking in the rhesus monkey.
The effect of 24-hr water deprivation and subsequent drinking on systemic fluid balance was determined in rhesus monkeys prepared with indwelling cardiac catheters. Significant intracellular and extracellular depletions, as indicated by increased plasma sodium concentrations, osmolality, and plasma protein concentrations, resulted from the deprivation. An early attenuation in rehydrational drinking rate (2--4 min) was not associated with changes in systemic fluid balance, which suggests presystemic influences on behavior at this time. When drinking terminated (10 min), however, plasma dilution was significant. In experiments in which monkeys were sham drinking (open gastric cannula), water but not isotonic saline infusions, given through an intestinal cannula, reduced drinking rate and produced significant plasma dilution. Intravenous water infusions reduced drinking to only a comparable extent despite more rapid and substantial plasma dilution. Thus, systemic absorption does not account entirely for the effect of intestinal water infusions on drinking. It is concluded that stimulation of mechanisms both presystemically (within the intestine or the hepatic portal circulation) and systemically is important in the control and termination of rehydrational drinking in this species.
Although useful in the management of malignant testicular tumours, alphafoetoprotein and human chromonic gonadotrophin are not perfect parameters of tumour bulk. In a series of 65 patients with marker-positive advanced disease, 23 showed the phenomenon of discordance of markers or dissociation from tumour response. Transplantable human malignant teratoma xenografts were established in immune-suppressed mice as models of the human disease. In the model system, it was demonstrated that tumour AFP concentration was reflected by AFP titres in the blood, but that tumour AFP (or blood AFP) did not correlate well with tumour size. One xenograft line illustrated the evolution of marker-negative tumour cells from a patient who was initially AFP-positive.
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Bombesin (BBS) is a tetradecapeptide originally isolated from amphibian skin1. BBS-like immunoactivity is widely distributed in mammalian gut2-5, and plasma levels have been shown to rise sharply following feeding (ref. 6 and V. Erspamer, personal communication). The physiological actions of BBS are unknown. We have previously shown that the classic gut hormone cholecystokinin (CCK) is a powerful and specific suppressor of food intake7-9. Although CCK and BBS lack common amino acid sequences, they have certain common actions on gut viscera10,11. We have now shown that BBS also suppresses food intake, and we compare its action with that of CCK.
The satiety effect of slow intravenous infusions of impure cholecystokinin (CCK) was investigated in 5 rhesus monkeys during sham feeding. CCK suppressed sham feeding. The dose for 50% inhibition of sham feeding was about 10 U/kg-hr; 20 U/kg-hr abolished sham feeding. No dose produced retching, vomiting, diarrhea or other behavioral signs of toxicity. These results demonstrate the potency of CCK for inhibiting feeding in the monkey when gastric, intestinal and postabsorptive mechanisms are not activated by ingested food.
Serial transplantation of an HCG-producing human testicular teratoma in immune-deprived mice is described. The xenografted tumour was compared to the tumour of origin in histology, immunohistochemistry (using an immune peroxidase technique to localize HCG) autoradiography, marker production and growth rate. It is concluded that the xenograft retained the characteristics of the original tumour with the exception of a reduction in HCG-producing elements at transplantation beyond 5 serial passages.
The size-distribution of normal human lymphocytes growing in tissue culture was measured with a Quantimet 720 image-analysing computer. The proportion of cells undergoing volumetric growth after phytohaemagglutinin (PHA) stimulation was dervived from a simple mathematical model describing the growth patterns of the cells up to the first mitotic division. The approach may have general application in biology as a method for measuring the proportion of growing cells by microscopy.
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