Morio Kanno

Effects of gastric acid stimulants and inhibitors on the activities of HCO3−-stimulated, Mg2+-dependent ATPase and carbonic anhydrase in rat gastric mucosa

Abstract The effects of gastric acid stimulants or inhibitors, in vivo and in vitro , on the activities of HCO 3 − -stimulated , Mg 2+ -dependent ATPase ( (HCO 3 − −Mg 2+ )-ATPase , ATP phosphohydrolase, EC 3.6.1.3) and carbonic anhydrase in rat gastric mucosa were investigated in order to elucidate the significance of and the functional relationship between these enzymes. 1. 1. Subcutaneous treatment with carbachol (25–400 μg/kg) produced gastric juice secretion in 3-h pylorus-ligated rats. This drug also increased the Mg 2+ -dependent ATPase (Mg 2+ -ATPase) and carbonic anhydrase activities of the homogenate of rat gastric mucosa. 2. 2. Subcutaneous treatment with gastric acid stimulants, i.e. carbachol, tetragastrin and histamine, stimulated gastric juice secretion in 3-h pylorus-ligated rats. These reagents also increased the Mg 2+ -ATPase and carbonic anhydrase activities in the mitochondrial fraction of rat gastric mucosa. 3. 3. Pretreatment with atropine (5 mg/kg, subcutaneously) or acetazolamide (20 mg/kg, subcutaneously) prevented the carbachol-induced increase of Mg-ATPase and carbonic anhydrase activities in the mitochondrial fraction. 4. 4. In vitro effects of gastric acid stimulants and inhibitors: Incubation of Mg 2+ -ATPase or (HCO 3 − -Mg 2+ )-ATPase with histamine (10 −3 M), carbachol (10 −3 M) or tetragastrin (10 −5 M) had no effect on the activity of the enzyme. These reagents did not stimulate the enzyme activity, directly. Thiocyanate (10 −2 M) inhibited the activity of the enzyme by about 30–40%. Ouabain (10 −2 M) had no effect on the activity. From these results, it was obvious that Mg 2+ -ATPase and carbonic anhydrase activities in the mitochondrial fraction of the gastric mucosa correlated with gastric acid secretion. It is likely that carbonic anhydrase is functionally linked to Mg 2+ -ATPase in rat gastric mucosa.

Selective β-adrenoceptor activities of tetrahydronaphthalene derivatives

Abstract Alpha - and beta -adrenoceptor activities of a group of tetralin derivatives prepared as fixed analogs of isoproterenol, adrenaline and noradrenaline were evaluated in vitro assays. All of the present compounds showed strong direct β-stimulating activity fairly selective for tracheal muscle. Activity of a trans isomer about the C(1)-C(2) bond was ten times higher than that of the cis isomer. None of the compounds tested had any practical α-adrenoceptor activity. Structure-activity interrelationships between the present series of compounds and some known adrenergic agonists are discussed.

A possible mechanism of choleretic action of 3-(2,4,5-triethoxybenzoyl)-propoionic acid (AA-149) in dogs

The choleretic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) was studied in anesthetized dogs. AA-149 produced a dose-dependent increase of the bile flow with both i.v. and intrajejunal administration of doses 1 mg/kg and higher. Biliary clearance of 14C-erythritol showed that AA-149 stimulated canalicular bile formation without enhancement of water secretion and/or inhibition of bile reabsorption in the biliary ductules and ducts. AA-149 did not increase the excretion of bile acids into the bile, but enhanced the excretion of the biliary electrolytes, in particular sodium ion, in proportion to an increase of the bile flow. About 3--4% of AA-149 administered i.v. was excreted into the bile during the first 1 h period, so that biliary AA-149 was insufficient to increase the bile flow via its osmotic effect. These results strongly suggest that the choleretic action of AA-149 is attributable to stimulation of a bile acid-independent bile formation in the canaliculi coupled with an active sodium transport system.

Biliary spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) in dogs.

The spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) on the biliary tract was investigated in anesthetized dogs. Intravenous administration of AA-149 at 2 mg/kg and higher doses produced a dose-dependent reduction in passage resistance through the choledochoduodenal junction and in gallbladder pressure, and a dose-dependent increase in bile flow. AA-149, like cholecystokinin, decreased biliary ductal pressure in spite of increasing the bile flow in dogs with ligation of the cystic duct of the gallbladder, whereas taurocholate increased the pressure as well as the bile flow. Moreover, the spasmic response of the choledochoduodenal junction to morphine was depressed strongly by AA-149, BUT NOT CONSISTENTLY BY ATROPINE. The effects of AA-149 were not influenced by pretreatment with atropine, phentolamine or propranolol. These findings strongly suggest that AA-149 relaxed the biliary tract and depressed the morphine-induced spasm by a mechanism different from those of anticholinergic and sympathomimetic agents.