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.
ETB2 receptor subtype stimulation relaxes the iris sphincter muscle