Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.

Abstract

A B S T R A C T It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method.Incubation of cortical homogenates with PTH for 10 min at 370C inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg"+-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100'C abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex.Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg"+ dependent and temperature dependent, and required preincubation at 370C. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase.All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of

Metabolic acidosis in patients receiving anticonvulsants

“…Acetazolamide and parathyroid hormone have been shown to inactivate CA-B in the kidney (Beck et al, 1975). However, in the present study no patient received acetazolamide in combination with the other drugs.…”

Inhibition of bicarbonate absorption by peptide hormones and cyclic adenosine monophosphate in rat medullary thick ascending limb.

“…It is possible, however, that the sensitivity of the adenylyl cyclase assay may be insufficient, or that performance of the assay in lysed cells under nonphysiological conditions may be inadequate to detect modest (-50%) changes in cyclase activity that may occur in intact cells and be physiologically significant. Alternatively, PTH could influence bicarbonate transport in thick ascending limbs by other mechanisms such as activation of Ca2l-dependent messenger systems (37,38), effects on prostaglandins, or inhibition of carbonic anhydrase (39).…”

Effects of Acetazolamide and Changes of Acid-Base Balance on the Content of Cyclic Nucleotides in the Rat Kidney

“…Furthermore, the effects of acetazolamide on kidney function were not accompanied by changes in tissue cAMP. Beck et al (1) suggested that the decrease of bi carbonate reabsorption in the kidney by para thyroid hormone is mediated by a cAMPinduced inhibition of carbonic anhydrase, although these results conflict with the data reported by Garg (2). Our results indicate that inhibition of bicarbonate reabsorption by acetazolamide is not linked to the cAMP sys tem.…”