Cholecystokinin revisited: CCK and the hunger trap in anorexia nervosa.

OBJECTIVE: Despite a number of studies in the past decades, the role of Cholecystokinin (CCK) in anorexia nervosa (AN) has remained uncertain. In this study a highly specific assay for the biologically active part of CCK was used in patients with bulimic as well as with the restricting type of AN who were followed over the course of weight gain. METHODS: Ten patients with restricting and 13 with bulimic AN were investigated upon admission (T0), after a weight gain of at least 2 kg on two consecutive weighting dates (T1), and during the last week before discharge (T2) from inpatient treatment in a specialized clinic. Blood samples were drawn under fasting conditions and 20 and 60 minutes following a standard meal (250 kcal). Data were compared to those of eight controls matched for sex and age. Gastrointestinal complaints of patients were measured by a questionnaire at each of the follow-up time points. RESULTS: At admission, AN patients exhibited CCK-levels similar to controls both prior to and after a test meal. Pre and post-meal CCK levels increased significantly after an initial weight gain but decreased again with further weight improvement. CCK release was somewhat lower in bulimic than in restricting type AN but both subgroups showed a similar profile. There was no significant association of CCK release to either initial weight or BMI, or their changes, but CCK levels at admission predicted gastrointestinal symptom improvement during therapy. CONCLUSIONS: Normal CCK profiles in AN at admission indicates hormonal responses adapted to low food intake while change of eating habits and weight gain results in initially increased CCK release (counteracting the attempts to alter eating behavior) that returns towards normal levels with continuous therapy.

Influence of acute exposure to high altitude on basal and postprandial plasma levels of gastroenteropancreatic peptides.

Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O(2)-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.

Endocrine correlates of acute nausea and vomiting.

This paper gives an overview of studies investigating endocrine changes in acute nausea and vomiting. The aetiology of nausea and vomiting is not fully understood, but it has been shown that different stress hormones are released into circulation during motion sickness. Studies with animals and humans have shown that acute nausea activates the hypothalamo-pituitary-adrenal axis and the neurohypophyseal system. So-called stress hormones, like adrenocorticotropic hormone, cortisol, and antidiuretic hormone, are released concomitant with nausea and vomiting in motion sickness, but do not seem to be involved in the aetiology of motion sickness. Nevertheless, plasma levels of stress hormones more or less correlate to the intensity of nausea related symptoms. Although gastroenteropancreatic hormones are involved in gastrointestinal motility, there are only few data describing their changes in response to acute nausea or vomiting.

mu-Opiate receptor agonists -- a new pharmacological approach to prevent motion sickness?

AIMS: Stress hormones might be involved in motion sickness. The influence of loperamide on kinetosis-induced nausea and stress hormone release was investigated in a placebo-controlled, cross-over study. METHODS: Standardized rotation around the vertical axis combined with head movements was used to induce nausea 3 h after 16 mg loperamide or placebo (n = 8). Plasma antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH) and nausea ratings were investigated. RESULTS: After loperamide nausea was significantly lower (P < 0.02). ACTH (P < 0.05) and ADH levels (P < 0.02) increased significantly in both settings, but were lower after loperamide. CONCLUSIONS: The susceptibility to develop kinetosis-induced nausea and stress hormone release is decreased by loperamide, although the site of action remains speculative.

Influence of microgravity on plasma levels of gastroenteropancreatic peptides: a case study.

BACKGROUND: No data are available about the short- or long-term influences of microgravity in space on the release of gastroenteropancreatic peptides, although these peptides are involved in the regulation of gastrointestinal functions. METHODS: Fasting plasma samples were gained during the EUROMIR-94 mission from a European Space Agency (ESA) astronaut who experienced no signs of space motion sickness in orbit. Plasma concentrations of nine gastroenteropancreatic peptides were measured with sensitive and specific radioimmunoassays. RESULTS: Fasting plasma levels of motilin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), and secretin were increased and plasma level of cholecystokinin (CCK) was decreased by acute exposure of the astronaut to microgravity. Chronic (4 wk) exposure caused an enhancement of plasma CCK, motilin, neurotensin, VIP, and insulin whereas plasma concentrations of PP, secretin, gastrin, and somatostatin showed no changes. During the 25-d stay on MIR station plasma levels of CCK, motilin, and neurotensin increased. Short-time body rotations caused an elevation of plasma levels of PP but decreased plasma motilin. CONCLUSIONS: As the influence of microgravity on the peptide levels was not uniform, an effect due to other factors (e.g., change in fluid balance or body weight) is unlikely. Moreover, adaptive changes of some peptides occurred during the stay in orbit. The release of PP and motilin seems to be very sensitive to rotation forces. These results have to be confirmed in more subjects in space to be able to link changes of gastroenteropancreatic peptide release to alterations of gastrointestinal functions.