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A.A. Rocha–Sousa, J. Saraiva, F. Falcão–Reis, A. Leite–Moreira; Relaxing Effect of Ghrelin on Iris Sphincter Muscle Is Not Mediated by GHSR–1a . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3685.
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Purpose: Ghrelin is a 28 aa peptide with important functions in smooth, cardiac and skeletal muscles. Some of its muscular effects seam mediated by a receptor other than GHRS–1a. The aim of this study was to investigate the mediation of its ocular effects by the GHSR–1a receptor. Methods: Rabbit (n=20) and Wistar rat (n=6) iris sphincter muscles, and rabbit iris dilator muscle (n=6) were dissected, mounted on a vertical organ bath containing a modified Krebs–Ringer solution (1.8 mM Ca2+; 35ºC) and attached to a force transducer. The effects of 1–5,Ghrelin (frGr, 10–9– 6*10–5M) on rabbit iris sphincter muscle pre–contracted with Charbacol (10–7M) were evaluated in the absence (n=7) or in the presence of D–Lys GHRP 6, a selective inhibitor of the Ghrelin receptor (GHS–R) (10–4M; n=6). The effects of 1–5,des–octanoil Ghrelin (dGr; 10–9– 6*10–5M), were also evaluated in iris sphincter muscles pre–contracted with Charbacol (rabbit;n=7;10–7M or rat;n=6;10–6M); and in rabbit dilator muscle (n=6) pre–contracted with epinephrin (10–4M). Only significant results (mean±SE, p<0.05) are given, and expressed as % changes from control. Results: When compared to control, frGr promoted a 34.1±12.1 % decrease in isometric tension for doses higher than 10–6 M. The inhibition of GHS–R increases and prolongs the relaxation elicited by frGr (118.1±21.1% vs 34.1±12.1% at 1.5 to 3’; p<0.05). DGr promoted also a 43.4±5.2 % decrease in isometric tension 1.5 to 3’ after its addition to the bathing solution, for doses higher than 10–6M (in rabbit sphincter muscle) and a 160.5±42.2 % decrease in rat. However in iris dilator muscle dGr did not have any significant effect (–3.1±12.1 %). Conclusions: Ghrelin relaxation of iris sphincter muscle is increased by the GHS–R inhibition and remains present when the muscle is stimulated by Des–octanoil–ghrelin. This effect is also present in rat muscle, but absent in iris rabbit dilator muscle.
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