PROSTAGLANDINS WITH VASODILATING EFFECTS INHIBIT CARBONIC-ANHYDRASE WHILE VASOCONSTRICTIVE PROSTAGLANDINS AND LEUKOTRIENS B4 AND C4 INCREASE CA ACTIVITY

Previous work carried out by our team in vitro regarding the relations hip between prostaglandins (PGs) and carbonic anhydrase (CA) has shown that prostaglandins E1 (PGE1), E2 (PGE2) and I2 (PGI2) inhibit purifi ed bovine red cell CA, as well as human red cell and gastric mucosa CA . This is a completion of our previous research work including kinetic and in vivo studies concerning the relationship between PGs and CA. T he relationship between CA and PGE1, E2 and I2, known for their vasodi lating and gastric acid secretion (GAS) reducing effects, on the one h and, and between CA and prostaglandin F2(alpha) (PGF2(alpha)), thrombo xans A2 (TXA2), and B4, C4 leukotriens (LTB4, LTC4), known for their v asoconstrictive effects, on the other hand, were studied in vitro. The in vivo studies followed changes induced by vasodilating PGs (misopro stol - analogue of PGE1, nalador - analogue of PGE2, ilomedin - analog ue of PGI2) and vasoconstrictive - minprostin analogue of PGF2(alpha) on red cell CA, correlated to modifications of arterial blood pressure (BP). Results obtained in vitro show that PGE1, E2, I2 inhibits basal CA activity, while PGF2(alpha), TXA2 and LTB4, LTC4 increase the acti vity of the enzyme. Kinetic assessments show that the inhibition and t he activation mechanism is a direct one of the non-competitive type lo cated on the active site of CA. Data obtained in vivo show that admini stration of a single therapeutic dose of misoprostol, nalador or ilome din inhibits basal activity of CA by 35 - 55% with corresponding decre ase of BP values. Administration of a single therapeutic dose of minpr ostin increases CA activity by 95% of its initial basal value, a rise accompanied by increase of BP values. These results lead to the conclu sion that reduction of CA activity induced by misoprostol, nalador and ilomedin correlates with decrease of BP values, while increase of CA activity induced by minprostin correlates with an increase of BP value s. The existence of a direct mechanism of activation and inhibition in duced upon CA by the 2 groups of PGs having opposite vascular effects as well as the activating effect of B4, C4 leukotriens, prove the invo lvement of CA in the vascular modifications in the organism. Consideri ng CA responsible for the variations of cellular pH in the organism, o ne may assume that changes induced by the direct effect of PGs and leu kotriens on CA could induce further modulation of the activity of the intracellular enzymatic system.