Reactive blue 2, an antagonist of rat P2Y4, increases K+ secretion in rat cochlea strial marginal cells.
Extracellular ATP decreases K+ secretion in strial marginal cells via apical P2Y4 receptors. We investigated the effect of reactive blue 2 (RB-2), an antagonist of rat P2Y4, on rat strial marginal cells using a voltage-sensitive vibrating probe. The application of RB-2 increased K+ secretion in a dose-dependent manner, and this increase was characterized as a peak followed by a partial relaxation to a steady-state. Moreover, this response was similar to that caused by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Suramin had no similar effect, except at high concentration. Thus, we tested the effects of these chemicals on P2Y4 receptors in strial marginal cells. Both RB-2 and DIDS had antagonistic activities at P2Y4, and the antagonist potency at P2Y4 paralleled the potency of K+ secretion. Interestingly, 2'- and 3'-O-(4-benzoyl-benzoyl)adenosine 5'-triphosphate (BzATP) exhibited an agonistic effect at P2Y4 receptor, which was blocked by RB-2, but not by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Based on these results, we speculate that direct and/or indirect inhibitory mechanisms between P2Y4 and KENQ1/KCNE1 K+ channels exist in strial marginal cell.
Lee
Jun Ho
JH
Department of Otolarygology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, Kyunggi-do, Republic of Korea. junlee@snu.ac.kr
Heo
Jeong-Hwa
JH
Chang
Sun O
SO
Kim
Chong-Sun
CS
Oh
Seung-Ha
SH
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D010498:Perilymph / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013316:Stria Vascularis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000494:pharmacology; D014732:Vibration
D004791:Enzyme Inhibitors; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D014227:Triazines; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; C012842:Cibacron Blue F 3GA; D013498:Suramin; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium; D014544:Uridine Triphosphate