Wadiah S Backer, Jalaluddin A Khan.
Effects of pharmacological agents on the activity of Rat Kidney Adenylyl Cyclase.
Pak J Med Sci Jan ;20(1):41-5.

Objective: To study the effect of both selective and nonselective activator and inhibitory agent on adenytyl cyclase in rat kidney. Design: Different concentrations of some pharmacological agents such as forskolin, nebularine, Ap4A, AP3A and caffeine were prepared. The effects of the agents on the activity of rat kidney adenylyl were determined. Methods: The crude extract obtained from rat kidney tissue was prepared and the specific activity of adenylyl cyclase in the crude extract was determined by using [2-H3] ATP as substrate which produced cAMP Different concentrations of important pharmacological agents as activators and inhibitors of enzyme were examined. The compounds selected were forskolin as a known activator of adenylyl cyclase and for comparison; nebularine, Ap4A, APA and caffeine were used. Results: The results obtained showed that the highest activity of adenylyl cyclase was at 100uM forskolin. The activity of enzyme was inhibited by nebularine as the concentration of agent was increased until at 50uM where the inhibition began to level off. The effect of caffeine at 10-300uM on the activity of adenylyl cyclase showed no significant effect on the enzyme activity in kidney tissue. APA showed no effect on the activity of adenylyl cyclase over the concentration range of 10-300uM, whereas, APA produced an inhibition effect on the enzyme activity at concentration 100uM. Conclusion: The important role of cyclic nucleotides in cell-signaling and metabolism control, evoke the activities and inhibitors of cyclase to play a potential physiological effects. As forskolin is well known activator of adenylyl cyclase, other pharmacological agents such as nebularine and Ap4A are found to be a potential inhibitors of cyclase, which highlight these compounds as treatment of mania, schizophrenia, seizure and parkinson`s diseases in which an increase of cAMP concentration has been demonstrated.

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