Effect of sulfonamides on the hypercalcemic response to vitamin D

Parathyroidectomized rats were fasted for twenty-four hours then treated with 10(6) units/kg of vitamin D3. Twelve hours later the animals were bilaterally nephrectomized and treated with either the appropriate control solution or one of the following: acetazolamide, methazolamide, ethoxzolamide or CL 13,850. Animals treated with the vitamin exhibited an increase in plasma calcium of approximately 5 mg/dl. This response was antagonized by treatment with acetazolamide, methazolamide or ethoxzolamide. These agents are all sulfonamide inhibitors of carbonic anhydrase. CL 13,850, a structural analog of acetazolamide that is devoid of enzyme inhibitory activity, was also devoid of inhibitory activity with respect to the hypercalcemic response to vitamin D3. Acetazolamide inhibited the response to the vitamin at doses yielding ultrafiltrable plasma drug concentrations of approximately 10(-5) to 10(-4) M. The hypercalcemic response observed following the administration of the active metabolite of vitamin D3 (1,25-dihydroxyvitamin D3) was attenuated by treatment with acetazolamide.