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., A. Rocha-Sousa ... [et al.]., and Obsahuje seznam literatury
Urocortin 2 (UCN2) is a peptide related to corticotropin-releasing factor, capable of activating CRF-R2. Among its multisystemic effects, it has actions in all 3 muscle subtypes. This study’s aim was to determine its potential role in two of the intrinsic eye muscle kinetics. Strips of iris sphincter (rabbit) and ciliary (bovine) muscles were dissected and mounted in isometric forcetransducer systems filled with aerated-solutions. Contraction was elicited using carbachol (10-6 M for iris sphincter, 10-5 M for ciliary muscle), prior adding to all testing substances. UCN2 induced relaxation in iris sphincter muscle, being the effect maximal at 10-7 M concentrations (-12.2 % variation vs. control). This effect was abolished with incubation of indomethacin, antisauvagine-30, chelerytrine and SQ22536, but preserved with L-nitro-L-arginine. In carbachol pre-stimulated ciliary muscle, UCN2 (10-5 M) enhanced contraction (maximal effect of 18.2 % increase vs. control). UCN2 is a new modulator of iris sphincter relaxation, dependent of CRF-R2 activation, synthesis of prostaglandins (COX pathway) and both adenylate cyclase and PKC signaling pathways, but independent of nitric oxide production. Regarding ciliary muscle, UCN2 enhances carbachol-induced contraction, in higher doses., M. Tavares-Silva, D. Ferreira, S. Cardoso, A. R. Raimundo, J. Barbosa-Breda, A. Leite-Moreira, A. Rocha-Sousa., and Obsahuje bibliografii