- Email: [email protected]
Prostaglandins and human gastric mucosa: Molecular aspects and protective properties
PROSTAGLANDINS PROSTAGLANDINS AND HUMAN TECTIVE PROPERTIES.
GASTRIC
MULLER
SIMON,
P., DPMMANN
H.G.,
MUCOSA
: MOLECULAR
ASPECTS
AND PRO-
B.
Medizinische Universitatsklinik Heidelberg, Gastroenterologische Abteilung, Bergheimerstr., 58, 6900 Heidelberg. Bethanien-Krankenhaus F.R.G.
Hamburg,
Martinistrasse
44, 2000 Hamburg
20,
Prostaglandins protect the stomach against a variety of noxious agents independently of effects on acid secretion, but the mechanism of this socalled "cytoprotection" in unknown. This unexplained activity is probably mediated by enhanced active HCO- and/or Cl--transport, both processes possibly involving cyclic AM? (Schiessel et al., Nature 283 : 671, 1980). Little is known about the cytoprotective properties of these compounds in man. We studied the effects of various prostaglandins on adenylate cyclase activity in biopsy specimens of corpus and antral mucosa, gastric acid output, the behaviour of transmucosal gastric potential diffeyastric DNArence (PD) foilowing aspirin etc. and aspirin-induced shedding in human volunteers. Adenylate cyclase activity was determined by the method of Salomon et al (Anal. Biochem. 58 : 541, 1974), basal acid output by rcutiae procedures, gastric transmucosal PD according to Andersson and Grossman (Gastroenterology 49 : 364, i965) and DNA-shedding as described by Croft. Adenylate cyclase in human corpus and antral biopsies was stimulated ), PGFZB, dose-dependently by cytoprotective PGE ,prostaqcyclin(PGI 15 (R) 15-methyl-PGF, not influence d2 or inhibited by PG?I2 and analogues of PGE1 and P@, (SC-29333). 16,16-dimethyl-PGE2 and the thiaprostaglandin EMD 33290 prevented the drop in gastric PD associated with 100@ mo aspirin or 50 ml of 4 mmol/l Na-taurocholate. The protective doses against aspirin were for 16,16dimethyl-PGE2 and EMD 33290 0.0001 and 0.70 bg/kg b.w., respectively. Against Na-taurocholate doses of 0.01 and 3.5 pg/kg b.w. were effective. By contrast, 20-100 times higher doses of both prostaglandin-analogues were necessary to inhibit gastric acid secretion. Half-maximal inhibition of BAO was achieved by 0.1 ug/kg b.w; of 16,16-dimethylPGE2 and 25 ug/kg b.w. of EMD 33290. The DNA-rise in gastric juice after 15OC mg of aspirin, not be prevented by 20 ug of 15 (R) 15-methyl-PGE2.
SUPPLEMENT TO VOL. 27
however,
could
129
GASTRIC
MULLER
SIMON,
P., DPMMANN
H.G.,
MUCOSA
: MOLECULAR
ASPECTS
AND PRO-
B.
Medizinische Universitatsklinik Heidelberg, Gastroenterologische Abteilung, Bergheimerstr., 58, 6900 Heidelberg. Bethanien-Krankenhaus F.R.G.
Hamburg,
Martinistrasse
44, 2000 Hamburg
20,
Prostaglandins protect the stomach against a variety of noxious agents independently of effects on acid secretion, but the mechanism of this socalled "cytoprotection" in unknown. This unexplained activity is probably mediated by enhanced active HCO- and/or Cl--transport, both processes possibly involving cyclic AM? (Schiessel et al., Nature 283 : 671, 1980). Little is known about the cytoprotective properties of these compounds in man. We studied the effects of various prostaglandins on adenylate cyclase activity in biopsy specimens of corpus and antral mucosa, gastric acid output, the behaviour of transmucosal gastric potential diffeyastric DNArence (PD) foilowing aspirin etc. and aspirin-induced shedding in human volunteers. Adenylate cyclase activity was determined by the method of Salomon et al (Anal. Biochem. 58 : 541, 1974), basal acid output by rcutiae procedures, gastric transmucosal PD according to Andersson and Grossman (Gastroenterology 49 : 364, i965) and DNA-shedding as described by Croft. Adenylate cyclase in human corpus and antral biopsies was stimulated ), PGFZB, dose-dependently by cytoprotective PGE ,prostaqcyclin(PGI 15 (R) 15-methyl-PGF, not influence d2 or inhibited by PG?I2 and analogues of PGE1 and P@, (SC-29333). 16,16-dimethyl-PGE2 and the thiaprostaglandin EMD 33290 prevented the drop in gastric PD associated with 100@ mo aspirin or 50 ml of 4 mmol/l Na-taurocholate. The protective doses against aspirin were for 16,16dimethyl-PGE2 and EMD 33290 0.0001 and 0.70 bg/kg b.w., respectively. Against Na-taurocholate doses of 0.01 and 3.5 pg/kg b.w. were effective. By contrast, 20-100 times higher doses of both prostaglandin-analogues were necessary to inhibit gastric acid secretion. Half-maximal inhibition of BAO was achieved by 0.1 ug/kg b.w; of 16,16-dimethylPGE2 and 25 ug/kg b.w. of EMD 33290. The DNA-rise in gastric juice after 15OC mg of aspirin, not be prevented by 20 ug of 15 (R) 15-methyl-PGE2.
SUPPLEMENT TO VOL. 27
however,
could
129