The presence of an active ETB1 receptor is essencial for ETB2 induced relaxation of the iris sphincter muscle

Abstract

Abstract Purpose: There are two subtypes of ETB receptors: ETB1 and ETB2. Stimulation of the latter relaxes iris sphincter. We investigated the interaction of the two ETB receptor subtypes in the iris sphincter muscle. Methods: Rabbit iris sphincter muscles (n=55) were dissected, mounted on a vertical organ attached to a force transducer and precontracted. The effects of ETB stimulation through (i) Endothelin‐1 (ET‐1;10e‐10–10e‐7M), in the presence of an ETA receptor antagonist (BQ‐123;10e‐5 M; n=7) (ii) sarafotoxin sc6 (SRTX‐c; [10e‐10–10e‐6M]; n=6) (iii) IRL‐1620 (ETB1 agonist; [10e‐10–10e‐7M; n=7) were evaluated. The effect of ETB stimulation was also evaluated in the presence of i) an ETA/ETB receptor antagonist, (PD145065;10e‐5M;n=4) ii) an ETB1 receptor antagonist, (RES‐701;10e‐6M;n=7) iii) an ETB2 receptor antagonist, (BQ‐788;10e‐5M;n=6) iv) a NOS inhibitor, (L‐nitro‐L‐arginine;L‐NA;10e‐5M;n=7); v) a COX inhibitor (indomethacin; indo;10e‐5M; n=10). Results: ETB stimulation by SRTX‐c or by ET‐1 in the presence of BQ‐123 promoted a concentration‐dependent relaxation of the rabbit sphincter muscles maximal at 10‐7M, averaging 10.8±2.03% and 9.35±1.79%, respectively. IRL‐1620 did not relax the iris sphincter muscle (0.91±5.45 %). The former was inhibited by RES‐701(‐0.09±2.23%) and BQ‐788 (‐2,30±2.04%). The effect was attenuated by PD145065 (5,71±0.98%) and by L‐NA (4.46±2.28%) or Indo (2.34±2.93%). Conclusions: ETB receptor stimulation relaxes the iris sphincter muscle, an effect that is mediated by the ETB2 subtype, through NO and prostaglandins release. However the presence of an active ETB1 receptor is essential for the activation of ETB2 receptor by sarafotoxin.