Gastrin level, elevated

Yes. The drug causes elevated levels of gastrin. However, this change is reversed upon discontinuation of therapy. 

McGuigan JE, Trudeau WL. Immunochemical measurement of elevated levels of gastrin in the serum of patients with pancreatic tumors of the Zollinger-Ellison variety. N Engl J Med 278 1308-1313,1968 idem. Little gastrin in normal serum, letter. NEnglJMed 280 509, 1969. 

A counterpart of evidence that CCK agonists are anxiogenic is to answer the question of whether the CCK system is functionally implicated in non-provoked symptoms of panic or anxiety. It is conceivable that endogenous variations of central and/or peripheral CCK activity may be a neurochemical concomitant of anxiety. It is interesting to mention that serum concentrations of gastrin, a CCK-B agonist, fluctuate in correlation with self-reported tension, conflict, and anxiety in psychiatrically healthy men (M. Feldman et al. 1992). Plasma CCK levels were markedly elevated in sportsmen before a competitive marathon run, as compared with CCK levels under control conditions (Phillip et al. 1992). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, and noradrenaline were also elevated and increased extensively after the running performance. However, CCK levels re-... 

Gastrin — Gastrin may possibly be important in other disease states. Elevation of serum gastrin levels have been reported in rheumatoid arthritis patients and elevated gastrin levels have been hypothesized to contribute towards maturity onset diabetes. ... 

Other potentially useful tests include antibody testing and serum gastrin levels. Positive anti-intrinsic factor antibodies may be present in approximately half of patients with pernicious anemia, but is highly specific for the disease. Additionally, an estimated 85% of patients have anti-parietal cell antibodies, but they are nonspecific, as 3% to 10% of healthy patients have these antibodies. Fasting serum gastrin levels are elevated in more than 70% of patients with cobalamin deficiency and may be useful in assessing patients with borderline... 

Histamine release from isolated ECL cells is also stimulated by PACAP as effectively as gastrin. This neuropeptide elevates intracellular Ca to a level similar to that of gastrin, with essentially the same time course as shown in the figure. 

In an isolated culture of ECL cells, a linear increase in gastrin-stimulated HDC activity was noted over 60 minutes. HDC levels were elevated up to threefold during this time. In a similar system of acutely isolated ECL cells, it has been noted that gastrin stimulated HDC activity with an ECso of 10- M and an EC of 10 M. Maximal stimulation resulted in a time-dependent increase of HDC activity, with linear kinetics up to 30 minutes, and no further increase between 30 and 60 minutes. In basophil leukemia cells, phorbol esters have been noted to increase HDC gene expression after 2 to 4 hours of incubation by 50% due to increased protein synthesis. The accelerated time course and amplified levels of HDC noted in ECL cells suggest that a second factor, such as posttranslational activation of HDC, might be involved, rather than only stimulation of HDC synthesis. 

The long-standing observation that cholinergic and gastrin stimulation of add secretion is potentiated by histamine or agents such as phosphodiesterase inhibitors, which elevate cAMP, suggests that cAMP and Ca, interact at some level. Thus, histamine, which acts primarily to elevate cAMP, has been shown... 

Activation of the H2 receptor by histamine injection or by elevation of histanrrine release by gastrin results in a transient increase in mRNA for the a subunit. H2 receptor antagonists prevent the gastrin- or histamine-dependent elevation of mRNA and appear to reduce mRNA to slightly below basal levels. These data were obtained in the rat, and the ATPase genes of this spedes possess cAMP- and Ca-responsive elements upstream of the coding sequence. 

Stimulation of acid secretion by the parietal cell is due mainly to gastrin-or pituary adenylate cyclase activating peptide (PACAP)-stimulated release of histamine from the enterochromaffin-like (ECL) cell of the fundic epithelium and activation of the H2 receptor. Direct stimulation by acetylcholine occurs at an M3 receptor on the parietal cell. The parietal cell also has a cholecystokinin B (CCK-B) receptor which appears to require permissive activation of the H2 receptor for elevation of parietal cell calcium. The H2 receptor is coupled to mainly Gs with elevation of cAMP but also to Gq, resulting in a small stimulation of intracellular calcium levels. The final event is activation of the H,K ATPase, which is in a resting, nonsecreting state in cytoplasmic membranes [24-26]. 

Smith JP, Wood JG, Solomon TE (1989) Elevated gastrin levels in patients with colon cancer or adenomatous polj s. Dig Dis Sci 34 171-174... 

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