Clinical application of an enzyme immunoassay for cholecystokinin-like immunoreactive substance for determination of the human plasma levels: the effect of metoclopramide on gastrointestinal peptides and stress-related hormones

Abstract

Metoclopramide, a prokinetic drug, is widely used to treat vomiting and nausea. Delayed gastric emptying and continual stress are considered important factors, among others, that induce nausea and vomiting. One gastrointestinal motility regulatory factor has been assumed to be the induction of changes in the levels of peptides such as gastrin, somatostatin, motilin, and cholecystokinin (CCK) in plasma. In contrast, adrenocorticotropic hormone (ACTH) and cortisol are used as indicators of stress. Here, we studied the effects of metoclopramide on human plasma gastrin-, somatostatin-, motilin-, and CCK-like immunoreactive substances (ISs) and ACTH-IS and cortisol under stress conditions using repetitive blood sampling in healthy subjects. Metoclopramide hydrochloride at a dose of 30 mg or placebo was orally administered to five healthy male volunteers. Blood samples were taken before and 20, 40, 60, 90, 120, 180, and 240 min after administration, subject to extracting procedures, and submitted to a highly sensitive enzyme immunoassay system. A single administration of metoclopramide caused significant increases in plasma somatostatin-IS levels compared with the placebo. Metoclopramide significantly decreased plasma gastrin- and suppressed ACTH-IS and cortisol levels compared with the placebo. We hypothesize that metoclopramide might have an accelerating gastric-emptying effect and a modulatory effect on the hypothalamo-pituitary-adrenal (HPA) axis and the autonomic nervous function. These effects might be beneficial in stress-related diseases, which suggest that this medicine has clinicopharmacological activities.

Combined administration of the mixture of honokiol and magnolol and ginger oil evokes antidepressant-like synergism in rats

“…The peptide hormone GAS is a member of the CCK family of peptides and stimulates gastric acid secretion (Rehfeld, 1981). Changes in gastrointestinal function have attracted attention, particularly the mechanisms responsible for alterations of gastrointestinal hormone induced by stress and depression (Itoh et al, 2005;Katagiri et al, 2006). Following the CUMS procedure, significant elevations in gastric mucosa CCK and serum GAS levels were observed in rats.…”

“…On the other hand, dysregulation of the gastrointestinal function involved response to stress and depression (Fossey and Lydiard, 1990;Katagiri, et al, 2006;Koh and Park, 2008). The active factor gastrin (GAS) identified originally as a gastric blood-borne stimulant of acid secretion (Edkins, 1906), is a classical gut peptide hormone.…”

Effects of Itopride Hydrochloride on Plasma Gut-Regulatory Peptide and Stress-Related Hormone Levels in Healthy Human Subjects

“…The study was carried out from 14: 00 to 18: 00. Blood sampling was performed to investigate circadian rhythms at 14: 00, 15: 30, and 18: 00 (three times) without administering a test medicine [9][10][11] .…”

“…Peptide levels in plasma were measured using highly sensitive enzyme immunoassays for gastrin- [9] , somatostatin- [10] , motilin- [12] , CCK- [11] , and ACTH-IS [13] , as previously described. Assays were performed using a delayed-addition method.…”