Sodium‐dependent regulation of sodium, potassium‐adenosine‐tri‐phosphatase (Na+, K+‐ATPase) activity in medullary thick ascending limb of Henle segments. Effect of cyclic‐adenosine‐monophosphate guanosine‐nucleotide‐binding‐protein activity and arginine vasopressin

Abstract

This study examine the regulation Na⁺, K⁺‐ATPase activity in the medullary thick ascending limb of Henle Na⁺, K⁺‐ATPase activity was determined in medullary thick ascending limb of Henle (mtal) segments dissected from rat kidneys. The sodium concentration in the medium (Na,) was 20 or 70 mM. Since the segments were permeabilized, intracellular Na⁺ (Na,) was assumed to be the same as Na₂. Dibuturyl cyclic adenosine monophosphate (dbcAMP) and forskolin inhibited Na⁺, K⁺‐ATPase activity independently of Na_m. Arginine vasopressin (AVP) receptors coupled to adenylate cyclase have been identified in the medullary thick ascending limb of Henle. At Na_m= 20 mMAVP caused a dose‐dependent inhibition of Na⁺, K⁺‐ATPase activity with a maximal effect (49%) at 10^‐8 m. This inhibition was abolished in the presence of the adenylate cyclase inhibitor 2,5‐dideoxyadenosine (2, 5‐DDA). AVP had no effect on Na⁺, K⁺‐ATPase activity in the mTAL at Na_m= 70 mM. The guanosine‐diphosphate analogue GDPβS inhibited Na⁺, K⁺‐ATPase activity at Na_m= 70 mM but not at Na_m= 20 mM.We conclude that increased cyclic adenosine monophosphate (CAMP) levels inhibit Na⁺, K⁺, ATPase activity in mTAL. AVP can, depending on Na₂ produce this effect by adenylate cyclase activation. The guanonine nucleotide binding protein G‐protein might be the site of Na⁺‐dependence.