title: Influence of cimetidine in low doses (less than ED50) on prostanoid production by human gastric mucosa in vitro.
abstract: Cimetidine has been defined as a cytoprotective agent and numerous studies have reported that it is able to influence prostaglandin production as well as mechanisms which protect the surface epithelium of the gastric mucosa. However, results have been contradictory and high drug concentrations contrasting the cytoprotection concept have been utilized. The present study tried to evaluate whether low concentrations (less than ED50) of cimetidine in vitro are able to modify prostanoids produced by gastric mucosa fragments. Thirteen patients without histological lesions were examined. Five mucosal biopsy specimens were obtained from the antrum in seven patients and from the body in another six patients. One biopsy was utilized for histological examination, while the remaining four specimens were incubated in the absence or in the presence of 5, 50 and 500 ng/ml of cimetidine, respectively. Concentrations of PGE2, 6-oxo-PGF1 alpha, PGF2 alpha and TXB2 in the incubate were determined by radioimmunoassay. Cimetidine at 50 ng/ml increased PGE2 production at the antrum level while 500 ng/ml of cimetidine increased PGF 2 alpha and TXB2 production at the body level. Furthermore, the drug dose was directly related to PGE2 production (at the antrum level) and TXB2 (at the body level). The differences in prostanoid production between the antrum and body could be due to the different cell composition of the two anatomical areas, and suggest that the effects of cimetidine are mediated through binding to H2-receptors. The authors conclude that cimetidine in low doses stimulates the net production of some but not all prostanoids, the observed effects varying with anatomical site.
authors.affiliation: Department of Internal Medicine, University of Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Andreone
authors.forename: M
authors.initials: M
authors.lastname: Baraldini
authors.forename: E
authors.initials: E
authors.lastname: Micaletti
authors.forename: C
authors.initials: C
authors.lastname: Cursaro
authors.forename: A
authors.initials: A
authors.lastname: Saggioro
authors.forename: A
authors.initials: A
authors.lastname: Della Monica
authors.forename: F
authors.initials: F
authors.lastname: Bortoluzzi
authors.forename: F
authors.initials: F
authors.lastname: Miglio
authors.forename: G
authors.initials: G
authors.lastname: Gasbarrini
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D002927:Cimetidine / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011506:Proteins / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D011453:Prostaglandins; D011506:Proteins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D002927:Cimetidine; D015237:Dinoprost; D015232:Dinoprostone