Enhancement of gastric mucus phospholipid secretion by an antiulcer agent, ebrotidine.
1. Rat gastric mucosal cells, subjected to phospholipid labeling by incubating the cell suspension in DMEM with [3H]choline, were exposed to different concentrations (0-150 microM) of H2-receptor antagonists, ebrotidine and ranitidine, and the phospholipid secretory responses were evaluated. 2. In the absence of the drugs, the secretion of choline-containing phospholipids over a 1 hr period averaged 3.97% of the total cellular labeled phospholipids. Ebrotidine caused a dose-dependent increase in the rate of phospholipid secretion which was most pronounced at 1 hr and persisted for at least 2 hr. The maximal effect was attained at 120 microM ebrotidine giving a 36% increase in phospholipid secretion. 3. The phospholipid secretory response to ebrotidine was accompanied by an increase in gastric mucosal cell cAMP level which reached a maximum value of 2.1-fold over that of controls at 1 hr. Ranitidine, in contrast, neither evoked increase in cAMP level nor caused any stimulation in phospholipid secretion. 4. The results indicate that the gastroprotective properties of ebrotidine are associated with the ability of the drug to elicit a rapid stimulation in gastric mucus phospholipid secretion, and that ranitidine does not possess such property.
Slomiany
B L
BL
Research Center, University of Medicine and Dentistry of New Jersey, Newark 07103-2400.
Piotrowski
E
E
Piotrowski
J
J
Zirvi
K A
KA
Liau
Y H
YH
Murty
V L
VL
Slomiany
A
A
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D001557:Benzenesulfonates; D010743:Phospholipids; D013844:Thiazoles; D011899:Ranitidine; D000242:Cyclic AMP; D002794:Choline; C075156:ebrotidine