INDOMETHACIN ABOLISHES THE EFFECT OF REDUCING
GASTRIC ACID SECRETION PRODUCED BY THE CARBONIC ANHYDRASE SPECIFIC INHIBITOR
Indomethacin (IMC) an inhibitor of cyclooxygenase reduces the prostaglandin biosynthesi 222d32c s and produces gastric lesions. Carbonic anhydrase (CA) inhibitors such as acetazolamide (ACZ) decreases basal and stimulated gastric acid secretion, depending on the dose (H.Janovitz et.al,Am.J.Physiol,171,325-30,1952)(I.Puscas, Ann.N.Y. Acad.Sci, 429, 587-91 ).
AIM: starting from our clinical observation that IMC antagonizes ACZ by a direct mechanism of action (I.Puscas et al.J.Pharmacol. Exp. Therap. 277, 3 -66,1996), in this paper we followed the associated effect of IMC to ACZ upon gastric acid secretion in human.
MATERIAL AND METHOD: 3 groups of healthy volunteers daily received during 5 days, as follows: Gr.1(N=61) IMC orally, 3mg/kg b.w.; Gr.2 (N=65) - ACZ, orally, 30 mg/kg b.w.; Gr.3(N=71)-orally, IMC, 3 mg/kg b.w.+ 30 mg ACZ. We determined in all groups before and after the 5 days administration both basal acid output (BAO) during 2 hours and erythrocyte CA II activity.
RESULTS: In Gr.1, IMC increases BAO from 2.11±0.81 to 4.67±1.02 mEq/h (p<0.005). CA II activity increases from 1.041±0.162 to 2.127±0.216 EU (p<0.002). In Gr.2, BAO decreases from 3.41±1.05 to 0.16±0.07 (p<0.001) and CA II activity decreases from 1.224±0.252 to 0.691±0.12 (p<0.005). In Gr.3 there are no significant modifications both in BAO and in CA II activity.
DISCUSSION AND CONCLUSIONS: The results prove that IMC antagonizes ACZ inhibitory effect both on BAO and concomitantly on CA II activity. Abolition by IMC of CA specific inhibitor effect after their associated administration suggests that CA is the situs of this interaction. IMC occupies the CA situs before ACZ and the latter could not dislocate the former. Our results explain this mechanism unelucidated so far and might put forward new pathways in this reasearch field.
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