Stimulatory effects of ghrelin on spontaneous contractions in the rat myometrium
Ghrelin, a recently isolated hormone, has been reported to have modulatory effects on smooth muscle contractility. In this study, we investigated the effects of ghrelin on spontaneous contractions in the rat uterus in vitro. Myometrium strips were removed from Wistar rats following decapitation and placed in a jacketed tissue bath. After initiation of spontaneous contractions, control contractions were recorded for 10 min and various concentrations of ghrelin were added to the tissue bath cumulatively. The Wilcoxon signed ranks test was used for statistical analysis. Application of ghrelin augmented the spontaneous contractions in myometrial strips. The mean peak amplitudes of contractions were 2.69 ± 0.32 g (n = 6), 2.71 ± 0.31 g (n = 6), 2.92 ± 0.36 g (n = 6), and 3.46 ± 0.24 g (n = 6) under control conditions and after application of 0.01 µM, 0.1 µM, and 1 µM ghrelin, respectively. The mean frequencies of contractions were 5.17 ± 0.75 (n = 6), 5.17 ± 0.75 (n = 6), 5.33 ± 0.48 (n = 6), and 8.0 ± 0.77 (n = 6) under control conditions and after application of 0.01 µM, 0.1 µM, and 1 µM ghrelin, respectively. The increase in amplitude and frequency of contractions was significant only after application of 1 µM ghrelin (P < 0.05). Data from this study demonstrated that ghrelin induces spontaneous contractions in a dose-dependent manner in the rat myometrium.
Stimulatory effects of ghrelin on spontaneous contractions in the rat myometrium
Ghrelin, a recently isolated hormone, has been reported to have modulatory effects on smooth muscle contractility. In this study, we investigated the effects of ghrelin on spontaneous contractions in the rat uterus in vitro. Myometrium strips were removed from Wistar rats following decapitation and placed in a jacketed tissue bath. After initiation of spontaneous contractions, control contractions were recorded for 10 min and various concentrations of ghrelin were added to the tissue bath cumulatively. The Wilcoxon signed ranks test was used for statistical analysis. Application of ghrelin augmented the spontaneous contractions in myometrial strips. The mean peak amplitudes of contractions were 2.69 ± 0.32 g (n = 6), 2.71 ± 0.31 g (n = 6), 2.92 ± 0.36 g (n = 6), and 3.46 ± 0.24 g (n = 6) under control conditions and after application of 0.01 µM, 0.1 µM, and 1 µM ghrelin, respectively. The mean frequencies of contractions were 5.17 ± 0.75 (n = 6), 5.17 ± 0.75 (n = 6), 5.33 ± 0.48 (n = 6), and 8.0 ± 0.77 (n = 6) under control conditions and after application of 0.01 µM, 0.1 µM, and 1 µM ghrelin, respectively. The increase in amplitude and frequency of contractions was significant only after application of 1 µM ghrelin (P < 0.05). Data from this study demonstrated that ghrelin induces spontaneous contractions in a dose-dependent manner in the rat myometrium.
___
- 1. Kojima M, Hosoda H, Date Y et al. Ghrelin is a growthhormone-releasing acylated peptide from stomach. Nature 402(6762): 656-660, 1999.
- 2. Arvat E, Di Vito L, Broglio F et al. Preliminary evidence that Ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans. J Endocrinol Invest 23(8): 493-495, 2000.
- 3. Date Y, Murakami N, Kojima M et al. Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats. Biochem Biophys Res Commun 275 (2): 477-480, 2000.
- 4. Tschop M, Smiley DL and Heiman ML. Ghrelin induces adiposity in rodents. Nature 407: 908-913, 2000.
- 5. Ariyasu H, Takaya K, Tagami T et al. Stomach is a major source of circulating ghrelin, feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J. Clin. Endocrinol. Metab 86(10): 4753-4758, 2001.
- 6. Caminos JE, Gualillo O, Lago F et al. The endogenous growth hormone secretagogue (ghrelin) is synthesized and secreted by chondrocytes, Endocrinol 146: 1285-1292, 2005.
- 7. Iglesias MJ, Pineiro R, Blanco M et al. Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes. Cardiovasc Res 62: 481-488, 2004.
- 8. Aydin S, Aydin S, Ozkan Y et al. Ghrelin is present in human colostrum, transitional and mature milk. Peptides 27( 4): 878- 882, 2006.
- 9. Caminos JE, Tena-Sempere M, Gaytan F et al. Expression of ghrelin in the cyclic and pregnant rat ovary. Endocrinol 144(4): 1594-1602, 2003
- 10. Gualillo O, Caminos J, Blanco M et al. Ghrelin, a novel placental-derived hormone. Endocrinol 142(2): 788-794, 2001.
- 11. Tanaka K, Minoura H, Isobe T et al. Ghrelin is involved in the decidualization of human endometrial stromal cells. J Clin Endocrinol Metab 88(5): 2335-2340, 2003.
- 12. Nakahara K, Hayashida T, Nakazato M, et el. Effect of chronic treatments with ghrelin on milk secretion in lactating rats. Biochem Biophys Res Commun 303(3): 751-755, 2003.
- 13. Papotti M, Ghe C, Cassoni P, et al. Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab 85(10): 3803-3807, 2000.
- 14. Wiley KE and Davenport AP. Comparison of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1. Br J Pharmacol 136(8): 1146-1152, 2002.
- 15. Okumura H, Nagaya N, Enomoto M et al. Vasodilatory effect of ghrelin, an endogenous peptide from the stomach. J Cardiovasc Pharmacol 39(6): 779-783, 2002.
- 16. Masuda Y, Tanaka T, Inomata N et al. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 276(3): 905-908, 2000.
- 17. Dimitrova DZ, Mihov DN, Wang R et al. Contractile effect of ghrelin on isolated guinea-pig renal arteries. Vascular Pharmacol 47 (1): 31-40, 2007.
- 18. Kohno D, Gao H, Muroya S et al. Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channeldependent mechanisms and cross-talk with leptin and orexin. Diabetes 52(4): 948-956, 2003.
- 19. Glavaski-Joksimovic A, Jeftinija K, Scanes CG et al. Stimulatory effect of ghrelin on isolated porcine somatotropes. Neuroendocrinol 77(6): 367-379, 2003.