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.
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 (Nam) was 20 or 70 mM. Since the segments were permeabilized, intracellular Na+ (Nai) was assumed to be the same as Nam. Dibuturyl cyclic adenosine monophosphate (dbcAMP) and forskolin inhibited Na+, K(+)-ATPase activity independently of Nam. Arginine vasopressin (AVP) receptors coupled to adenylate cyclase have been identified in the medullary thick ascending limb of Henle. At Nam = 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 Nam = 70 mM. The guanosine-diphosphate analogue GDP beta S inhibited Na+, K(+)-ATPase activity at Nam = 70 mM but not at Nam = 20 mM. We conclude that increased cyclic adenosine monophosphate (cAMP) levels inhibit Na+, K(+)-ATPase activity in mTAL. AVP can, depending on Nai, produce this effect by adenylate cyclase activation. The guanonine nucleotide binding protein G-protein might be the site of Na(+)-dependence.
Fryckstedt
J
J
Department of Pediatrics, Karolinska Institutet, Sweden.
Aperia
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D002373:Cyclic AMP Receptor Protein; D019204:GTP-Binding Proteins / Q000502:physiology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000378:metabolism; D008138:Loop of Henle / Q000201:enzymology*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology
D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D013873:Thionucleotides; D001127:Arginine Vasopressin; D006153:Guanosine Diphosphate; D003994:Bucladesine; C023427:guanosine 5'-O-(2-thiodiphosphate); D000255:Adenosine Triphosphate; D012964:Sodium; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase