Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and dilator muscles

Abstract

Ghrelin is a recently described acylated peptide, which works as a somatosecretagogue and has described effects on the smooth, skeletal and cardiac muscle. We examined the production and effects of ghrelin on relaxation of the iris muscles. Contractile effects of 1e5 human ghrelin (frGhr, 10 À9 À6 Â 10 À5 M) and 1e5 human des-octanoyl-ghrelin (d-frGhr; 10 À9 À6 Â 10 À5 M) were tested on iris rabbit sphincter (n ¼ 11 frGhr; n ¼ 7 d-frGhr), dilator (n ¼ 6 frGhr; n ¼ 6 d-frGhr) and rat sphincter (n ¼ 6 frGhr; n ¼ 8 d-frGhr) precontracted muscles. On rabbit sphincter the effect of frGhr was also tested in presence of: i) L-NA (10GHRP6 (10 À4 M; n ¼ 6); and iv) apamin þ carybdotoxin (10 À6 M; n ¼ 6). Furthermore, on rabbit dilator the effect of frGhr was tested in presence of DLys 3 GHRP6 (10 À4 M; n ¼ 7). Finally, ghrelin mRNA production was assessed by ''in situ'' hybridization in Wistar rat eyes (n ¼ 8). In all muscles, frGhr promoted a concentration-dependent relaxation, maximal at 6 Â 10 À5 M, 1.5e3 min after its addition, decreasing tension by 34.1 AE 12.1%, 25.8 AE 4.8% and 52.1 AE 10.3% in the rabbit sphincter, dilator and rat sphincter, respectively. In the rabbit sphincter the relaxing effects of frGhr were: (i) enhanced in presence of DLys 3 GHRP6 (118.1 AE 21.1%); (ii) blunted by indomethacin; and (iii) not altered by apamin þ carybdotoxin (36.4 AE 14.4%) or L-NA (52.4 AE 11.4%). Relaxing effects of d-frGhr in rabbit (43.3 AE 5.2%) and rat (77.1 AE 15.3%) sphincter muscles were similar to those of frGhr. In rabbit dilator muscle, d-frGhr did not significantly alter active tension and the relaxing effect of frGhr was blunted by GHSR-1a blockage. Ghrelin mRNA was identified in iris posterior epithelium. In conclusion, ghrelin is a novel, locally produced, relaxing agent of iris dilator and sphincter muscles, an effect that is mediated by GHSR-1a in the former, but not in the latter. Furthermore, in the sphincter it seems to be mediated by prostaglandins, but not by NO or K Ca channels.

Ghrelin, des-acyl ghrelin and obestatin: Three pieces of the same puzzle

“…Des-acyl ghrelin does not influence sleep, memory, behavior nor milk secretion [21,108,154]. Relaxing effects of des-acyl ghrelin in iris sphincter muscle were similar to those of ghrelin, while in dilator muscle, des-acyl ghrelin did not significantly alter active tension and the relaxing effect of ghrelin was blunted by GHSR-1a blockage [122].…”

“…The continuously increasing list includes stimulation of prolactin, ACTH, AVP [103,106], promotion of slow-wave sleep [154], memory retention and anxiety-like behavior [21] and stimulation of milk secretion [108]. Recently, we have reported that ghrelin is expressed in the iris and induces relaxation of iris sphincter and dilator muscles [122]. Des-acyl ghrelin does not influence sleep, memory, behavior nor milk secretion [21,108,154].…”

Diabetes, Ghrelin And Related Peptides: From Pathophysiology To Vasculopathy

“…Both acylated and non-acylated forms of ghrelin can mediate some of ghrelin effects while only the acylated form can bind to GHSR-1a. The activation of cyclooxygenase by non-acylated, acylated and truncated forms of ghrelin indicates the existence of another active receptor different from GHSR-1a [10,[46][47][48]. CD36, a multifunctional B-type scavenger receptor expressed in the adipose tissue, platelets, monocytes, macrophages, denditric cells, microvascular endothelium and myocardium [49], is implicated in ghrelin's role in the protection of the myocardium from ischemia [50].…”

“…Ghrelin is also produced in the X/A cells of the intestine and in some others tissues such as the pancreas, kidney, placenta, lymphatics, *Address correspondence to this author at the Department of Physiology, Faculty of Medicine, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Tel: +351 225513644; Fax: +351 225513646; E.mail: arsousa@med.up.pt # Both authors had the same contribution to the article gonads, adrenal, thyroid gland, heart, lung, pituitary, hypothalamus, eye [10], human B-and T-lymphocytes, neutrophils [1,[10][11][12], morula, blastocyts and embryos [13]. Ghelardoni observed that ghrelin gene expression and its protein were, in some tissues, dissociated [14].…”

Systemic administration of ghrelin did not restore angiogenesis in hindlimb ischemia in control and diet-induced obese mice

“…Ghrelin is a novel growth hormone released mainly from the stomach (9). It is involved in food intake, regulation of appetite and energy homeostasis, in addition modulation of gastrointestinal, cardiovascular, pulmonary and immune functions, cell proliferation/apoptosis (10).…”