Adenosine stimulates the basolateral 50 pS K channels in the thick ascending limb of the rat kidney.
We used the patch-clamp technique to examine the effect of adenosine on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. A 50-pS inwardly rectifying K channel was detected in the basolateral membrane, and the channel activity was decreased by hyperpolarization. Application of adenosine (10 microM) increased the activity of basolateral 50 pS K channels, defined by NP(o), from 0.21 to 0.41. The effect of adenosine on the 50 pS K channels was mimicked by cyclohexyladenosine (CHA), which increased channel activity by a dose-dependent manner. However, inhibition of the A1 adenosine receptor with 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) failed to block the effect of CHA. In contrast, application of 8-(3-chlorostyryl) caffeine (CSC), an A2 adenosine antagonist, abolished the stimulatory effect of CHA. The possibility that the effect of adenosine and adenosine analog on the basolateral 50 pS K channel was the result of activation of the A2 adenosine receptor was also suggested by the observation that application of CGS-21680, a selected A(2A) adenosine receptor agonist, increased the channel activity. Also, inhibition of PKA with N-[2-(methylamino)ethyl]-5-isoquinoline sulfonamide-2HC1 abolished the stimulatory effect of CHA on the basolateral 50 pS K channel. Moreover, addition of the membrane-permeable cAMP analog increases the activity of 50 pS K channels. We conclude that adenosine activates the 50 pS K channel in the basolateral membrane of the TAL and the stimulatory effect is mainly mediated by a PKA-dependent pathway via the A2 adenosine receptor in the TAL.
Gu
Ruimin
R
Dept. of Pharmacology, Harbin Medical University, Harbin 150086, China.
Wang
Jing
J
Zhang
Yunhong
Y
Li
Wennan
W
Xu
Ying
Y
Shan
Hongli
H
Wang
Wen-Hui
WH
Yang
Baofeng
B
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists; D000262:Adenylyl Cyclases / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043683:Receptors, Adenosine A2 / Q000187:drug effects; D013268:Stimulation, Chemical; D014970:Xanthines / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D010627:Phenethylamines; D015221:Potassium Channels; D043683:Receptors, Adenosine A2; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C081320:8-(3-chlorostyryl)caffeine; C027513:N(6)-cyclohexyladenosine; D002110:Caffeine; D003994:Bucladesine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000262:Adenylyl Cyclases; D000241:Adenosine