title: Dietary K intake regulates the response of apical K channels to adenosine in the thick ascending limb.
abstract: We used the patch-clamp technique to study the effect of adenosine on the apical 70-pS K channel in the thick ascending limb (TAL) of the rat kidney. Application of 1 microM cyclohexyladenosine (CHA), an adenosine analog, stimulated apical 70-pS K channel activity and increased the product of channel open probability and channel number (NP(o)) from 0.34 to 0.7. Also, addition of CGS-21680, a specific A(2a) adenosine receptor agonist, mimicked the effect of CHA and increased NP(o) from 0.33 to 0.77. The stimulatory effect of CHA and CGS-21680 was completely blocked by H89, an inhibitor of protein kinase A (PKA), or by inhibition of adenylate cyclase with SQ-22536. This suggests that the stimulatory effect of adenosine analogs is mediated by a PKA-dependent pathway. The effect of adenosine analog was almost absent in the TAL from rats on a K-deficient (KD) diet for 7 days. Application of DDMS, an agent that inhibits cytochrome P-450 hydrolase, not only significantly increased the activity of the 70-pS K channel but also restored the stimulatory effect of CHA on the 70-pS K channel in the TAL from rats on a KD diet. Also, the effect of CHA was absent in the presence of 20-HETE. Inhibition of PKA blocked the stimulatory effect of CHA on the apical 70-pS K channel in the presence of DDMS in the TAL from rats on a KD diet. We conclude that stimulation of adenosine receptor increases the apical 70-pS K channel activity via a PKA-dependent pathway and that the effect of adenosine on the apical 70-pS K channel is suppressed by low-K intake. Moreover, the diminished response to adenosine is the result of increase in 20-HETE formation, which inhibits the cAMP-dependent pathway in the TAL from rats on a KD diet.
authors.affiliation: Dept. of Pharmacology, BSB Rm. 537, New York Medical College, Valhalla, NY 10595, USA. wenhui_wang@nymc.edu
authors.forename: Dimin
authors.initials: D
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Wang
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058908:Adenosine A2 Receptor Agonists; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D017419:Potassium, Dietary / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007546:Isoquinolines; D010627:Phenethylamines; D015221:Potassium Channels; D017419:Potassium, Dietary; D013449:Sulfonamides; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C027513:N(6)-cyclohexyladenosine; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D000241:Adenosine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide