Effects of Analgetics and Non-Steroidal Anti-Inflammatory Drugs on Permeability of Toad Urinary Bladder

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In order to study the effect of some analgetics and anti-inflammatory drugs on permeability of biological membrane, such analgetics or non-steroidal anti-inflammatory drugs as acetanalide, acetophenetidine, acetaminophen, aminopyrine, phenylbutazone, oxyphenbutazone, benzydamine hydrochloride, flufenamic acid, mepirizole, salicylic acid, mefenamic acid, indomethacin and ibufenac, were added to the bicarbonate Ringer's solutions which were bathing the urinary bladder of toad, Bufo bufo japonicus; and the changes in net water flux (Bentley), SCC, P. D. and conductance (Ussing & Zerahn) were measured. 1.4×10-3-10-4M Benzydamine hydrochloride and flufenamic acid added to the serosal side inhibited the effect of vasopressin on water permeability, but mepirizole and salicylic acid did not show any significant effect. In contrast, all the other drugs potentiated the effect of vasopressin and, even in the absence of vasopressin, enhanced water permeability which was completely inhibited by 10-5M epinephrine or 10-4M 2, 4-DNP. The effect of cyclic 3', 5'-AMP on water permeability was inhibited by addition of oxyphenbutazone and benzydamine hydrochloride to the serosal side, but slightly enhanced by aminopyrine and acetaminophen. Furthermore 5×10-3M oxyphenbutazone on the serosal side inhibited the effect of vasopressin, although this drug in a lower concentration enhanced the effect of vasopressin. When it was added to the mucosal side, the effects of vasopressin and theophylline were also potentiated. Almost the same results were obtained in case of mefenamic acid. On the contrary, benzydamine hydrochloride inhibited the effect when added either to the serosal side or to the mucosal side, and also depressed the effect of theophylline. Short-circuit current, membrane potential difference and conductance (SCC/P. D.) were depressed when 5×10-5M mefenamic acid and 5×10-4M benzydamine hydrochloride were added either to the serosal or to the mucosal side. In contrast, oxyphenbutazone depressed these electrical properties only when added to the serosal side. From the above results, it could be concluded that non-steroidal anti-inflammatory drugs may be classified into at least three groups from the viewpoint of difference in their effects on osmotic flow of water which were induced by vasopressin, and also suggested that some direct effects of these drugs on cell membrane may play an important role in the mode of action of anti-inflammation.
Japan Society of Clinical Chemistryの論文

Effects of Analgetics and Non-Steroidal Anti-Inflammatory Drugs on Permeability of Toad Urinary Bladder

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