Failure of 16,16-dimethyl PGE2 to prevent inhibitory effect of ethanol on sodium transport in canine gastric mucosa.
By use of an in vitro canine gastric mucosal preparation, we evaluated the effects of ethanol (2, 4, 6, and 8%, vol/vol) and indomethacin (2.2 X 10(-4)M), with and without 16,16-dimethyl PGE2 pretreatment, on net sodium transport (JNanet) (mucosal to serosal) across gastric epithelium. Although administration of 2 or 4% ethanol to the mucosal bathing solution had no appreciable inhibitory effects on sodium transport, 6 and 8% ethanol and indomethacin significantly inhibited JNanet when compared with untreated control mucosa. This effect was accompanied by inhibition of transmucosal potential difference (PD) and short-circuit current (Isc). In other mucosae exposed to dimethyl PGE2 (8 X 10(-6) M) in the serosal bathing solution, significant increases in JNanet, PD, and Isc were noted when compared with control mucosa. Addition of 6 or 8% ethanol to the mucosal solution of dimethyl PGE2-pretreated tissue resulted in significant decreases in PD, Isc, and JNanet below control values that were not significantly different from mucosa exposed to 6 and 8% ethanol without PG pretreatment. When indomethacin was added to the mucosal solution following dimethyl PGE2 pretreatment, only slight decreases in PD and Isc below control levels were observed, and the inhibitory effects on JNanet induced by indomethacin without such treatment were abolished. These findings suggest that stimulation of JNanet by prostaglandin may play a role in its ability to prevent indomethacin damage to gastric epithelium but does not appear to be of importance in mediating protection against ethanol damage.
Miller
T A
TA
Henagan
J M
JM
Kuo
Y J
YJ
Shanbour
L L
LL
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004285:Dogs; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011292:Premedication; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013997:Time Factors
D007473:Ion Channels; D011459:Prostaglandins E, Synthetic; D000431:Ethanol; D012964:Sodium; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin