ETB2 Receptor Subtype Stimulation Relaxes the Iris Sphincter Muscle

Abstract

Effects of ETB receptor stimulation and its subcellular pathways were evaluated in carbachol pre-contracted rabbit iris sphincter muscles (n=51). ETB stimulation with sarafotoxin (SRTX-c; 10(-10)-10(-6) M) was tested in the absence (n=7) or presence of 10(-5) M of: BQ-788 (ETB2 receptor antagonist; n=6), L-NA (NOS inhibitor; n=7) or indomethacin (cyclooxygenase inhibitor; n=10). Effects of ETB stimulation by endothelin-1 (ET-1; 10-(10)-10(-7) M) in the presence of an ETA receptor antagonist (BQ-123; 10(-5) M; n=7) and of ETB1 stimulation by IRL-1620 (10-(10)-10(-7) M; n=7) were also tested. Finally, the effects of SRTX-c (10(-9)-10(-7) M) in electric field stimulation (EFS) contraction were evaluated (n=7). ETB receptor stimulation by SRTX-c or ET-1 in presence of BQ-123 promoted a concentration-dependent relaxation of the rabbit iris sphincter muscle by 10.8 +/- 2.0 % and 9.4 +/- 1.8 %, respectively. This effect was blocked by BQ-788 (-2.3 +/- 2.0 %), L-NA (4.5 +/- 2.3 %) or indomethacin (2.3 +/- 2.9 %). Selective ETB1 stimulation by IRL-1620 did not relax the iris sphincter muscle (0.9 +/- 5.4 %). EFS elicited contraction was not altered by SRTX-c. In conclusion, ETB receptor stimulation relaxes the carbachol precontracted iris sphincter muscle, an effect that is mediated by the ETB2 receptor subtype, through NO and the release of prostaglandins.