Stimulation Of Adenosine A1 Receptor Inhibits The Basolateral 50 Ps K Channels In The Thick Ascending Limb Of Rat Kidney

We used the patch‐clamp technique to study the effect of stimulation of Adenosine A 1 receptor on the basolateral 50 pS K channels in the thick ascending limb (TAL) of rat kidney. 100nM or 200nM Adenosine (ADO) inhibited the basolateral 50 pS K channels. However, 400nM, 800nM and 1μM Adenosine did not decrease the 50 pS K channel activity. Adenosine's effect was mimicked by the specific adenosine A 1 receptor agonist Cyclohexyladenosine (CHA). Inhibition of adenosine A 1 receptor with 8‐cyclopentyl‐1, 3‐dipropylxanthine (DPCPX), adenosine A 1 receptor antagonist, abolished the inhibitory effect of 100nM adenosine. Stimulation of adenosine A 1 receptor did not decrease the activity of basolateral 50 pS K channels in the presence of the inhibitor of phospholipase C (PLC), U‐73122 or the inhibitor of protein kinase‐C (PKC), Calphostin‐C, respectively. The mitogen‐activated protein kinase ( MAPK) inhibitors of PD98059 (ERK) or SB202190 (p38) increased the 50 pS K channel activity. PD98059 abolished the inhibitory effect of CHA. CHA decreased the 50 pS K channel activity in the presence of SB202190. These studies show that the inhibitory effect of 100nM adenosine on the basolateral 50 pS K channels, coupled adenosine A 1 receptor, is mediated by PLC‐PKC and MAPK (ERK) pathways in the thick ascending limb of the rat kidney. The work is supported by Chinese National Natural Science Foundation 30770800, 31071017 and 31171110.