The effects of apelin on myometrium contractions in pregnant rats

Emine Kacar; Zubeyde Ercan; Ihsan Serhatlioglu; Aysegul Sumer; Haluk Kelestimur; Selim Kutlu

doi:10.14715/cmb/2018.64.11.13

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Vol. 64 No. 11: Issue 11

Issue Published : August 31, 2018

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The effects of apelin on myometrium contractions in pregnant rats

https://doi.org/10.14715/cmb/2018.64.11.13

Emine Kacar

Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey

Zubeyde Ercan

Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey

Ihsan Serhatlioglu

Department of Biophysics, Faculty of Medicine, Firat University, Elazig, Turkey

Aysegul Sumer

Department of Nursing, Faculty of Health, Recep Tayyip Erdoğan University, Rize, Turkey

Haluk Kelestimur

Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey

Selim Kutlu

Department of Physiology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

Corresponding Author(s) : Emine Kacar

dreminekacar@hotmail.com

Cellular and Molecular Biology, Vol. 64 No. 11: Issue 11
Article Published : August 30, 2018

Abstract

Apelin, which is a new hormone, is secreted especially in the brain by hypothalamus as well as by many other organs like the stomach, fat tissue, and the heart. For apelin, whose possible effects on many bodily functions like the endocrine system, cardiovascular system and metabolic activities are still under investigation, the reproductive system is also an important target area. The purpose of the present study was to investigate the effects of plasma apelin levels in rats that were in diestrus, pregnancy and lactation periods, and to examine its possible effects on myometrium contractions of pregnant rats and non-pregnant rats that were in diestrus period. The plasma apelin concentrations in female adult Wistar rats were determined with the ELISA method in the diestrus period, and on the 12th, 18th, and 21st days of the pregnancy, and on the 2nd and 10th days of lactation (n=7 for each group). In addition, the effect of apelin at 0.01, 0.1, 1 and 10 Î¼M doses on isometric contractions in the rat uterus on the 21st day of pregnancy and in diestrus period was tested by using isolated organ bath. This protocol was repeated under conditions that were pre-treated with protein kinase C inhibitor in calcium-free medium, and the possible effect of apelin on contractions and the mechanisms that might mediate this effect were investigated. When plasma apelin levels were compared with the rats in diestrus period, the apelin concentrations in the 21-day pregnancy group were high at a significant level (p<0.05); and low at a significant level in the 2-day lactation group (p<0.05). In myometrium contraction trials, it was observed that apelin induced the contractions. Apelin increased the frequency of the myometrium contractions at a significant level when applied at 1 Î¼M and 10 Î¼M concentrations (p<0.05 and p<0.001). Only after the apelin application at 10 Î¼M concentration did the amplitude of the contractions increase at a significant level (p<0.01). In the myometrium of the rats that were on the 21st day of pregnancy, the frequency of the contractions was statistically significant at 0.1 Î¼M, 1 Î¼M and 10 Î¼M doses (p<0.01). In addition, the amplitude of the contractions increased at a statistically significant level at 1 Î¼M and 10 Î¼M dose application (p<0.05 and p<0.01, respectively). The apelin application induced the contractions in calcium-free medium. When apelin was applied after the pre-application with protein kinase C inhibitor, no contractions were observed. The present study showed that apelin levels were increased at the end of pregnancy in rats, and the hormone induced the uterus contractions. This effect does not occur with protein kinase C inhibitor and in calcium-free medium, which shows that protein kinase C pathway might play a role in these mechanism. These findings show that apelin might be an endogenous peptide that plays a role on uterine contractions at birth in rats.

Keywords

Apelin Contraction Myometrium Pregnancy Tissue Bath.

Kacar, E., Ercan, Z., Serhatlioglu, I., Sumer, A., Kelestimur, H., & Kutlu, S. (2018). The effects of apelin on myometrium contractions in pregnant rats. Cellular and Molecular Biology, 64(11), 74–79. https://doi.org/10.14715/cmb/2018.64.11.13

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References

Reference
Tatemoto K, Fujii R, Fujino M, Fujii R, Kakegawa T, Zou MX et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 1998; 251: 471–6.
Shin K, Chapman NA, Sarker M, Kenward C, Huang SK, Weatherbee-Martin N et al. Bioactivity of the putative apelin proprotein expands the repertoire of apelin receptor ligands. Biochim Biophys Acta. 2017 S0304-4165(17)30169-1. doi: 10.1016/j.bbagen.2017.05.017.
Medhurst AD, Davis RP, Ellis C, Davis RP, Ellis C, Winborn KY et al. Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin. J Neurochem 2003; 84 (5): 1162-72.
Kleinz MJ, Davenport AP. Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Regul Pept 2004; 118(3): 119-25.
De Falco M, Artigiano F, Cavallotti I, Cavallotti I, Artigiano F, Esposito V et al. Apelin expression in normal human tissues. In Vivo 2002; 16: 333–336.
Ferrante C, Orlando G, Recinella L, Leone S, Chiavaroli A, Di Nisio C et al. Central apelin-13 administration modulates hypothalamic control of feeding. J Biol Regul Homeost Agents. 2016; 30(3):883-88.
Rak A, Drwal E, Rame C, Knapczyk-Stwora K, SÅ‚omczyÅ„ska M, Dupont J et al. Expression of apelin and apelin receptor (APJ) in porcine ovarian follicles and in vitro effect of apelin on steroidogenesis and proliferation through APJ activation and different signaling pathways. Theriogenology. 2017; 96:126-35.
Cobellis L, De Falco M, Mastrogiacomo A, Colacurci N, De Luca A et al. Modulation of apelin and APJ receptor in normal and preeclampsia-complicated placentas. Histol Histopathol 2007; 22: 1-8.
Habata Y, Fujii R, Fujino M, Fukusumi S, Kawamata Y, Hinuma S et al. Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum. Biochim Biophys Act. 1999; 1452: 25-35.
Malamitsi-Puchner A, Gourgiotis D, Boutsikou M, Baka S, Hassiakos D, Briana DD. Circulating apelin concentrations in mother/infant pairs at term. Acta Paediatr 2007; 96: 1751-4.
Meng J, Casey PJ. Signaling through Gz. Handbook of cell signaling, edited by Bradshaw RA and Dennis EA. Boston, MA: Academic, 2004:601-604.
Challis JRG1, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev. 2000;21(5):514-50.
Liu QF, Yu HW, Sun LL, You L, Tao GZ, Qu BZ. Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and ć°NTRACELLULAR signaling pathways. Biochem Biophys Res Commun. 2015 ;468(4):617-21.
Adebiyi A, Adaikan PG, Prasad RN. Effect of benzyl isothiocyanate on spontaneous and induced force of rat uterine contraction. Pharmacol Res. 2004; 49: 415-22.
Shmygol A, Gullam J, Blanks A, Thornton S. Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility. Acta Pharmacol Sin 2006; 27: 827-32.
Kawarabayashi T, Tsukamoto T, Shojo H, Nakamura S, Sugimori H. Changes in responsiveness of freshly isolated longitudinal muscle cells from rat uterus towards oxytocin during gestation: contractility and calcium signaling. Mol Cell Endocrinol. 1997; 128: 77-84.
Van Mieghem T1, van Bree R, Van Herck E, at al. Maternal apelin physiology during rat pregnancy: the role of the placenta. Placenta. 2010;31(8):725-30.
Telejko B, Kuzmicki M, Wawrusiewicz-Kurylonek N, Szamatowicz J, Nikolajuk A, Zonenberg A, et al. Plasma apelin levels and apelin/APJ mRNA expression in patients with gestational diabetes mellitus. Diabetes Res Clin Pract. 2010; 87: 176-83.
Kourtis A, Gkiomisi A, Mouzaki M, Makedou K, Anastasilakis AD, Toulis KA, et, al. Apelin levels in normal pregnancy. Clin Endocrinol Ox. 2011; 3: 367-71
Van Mieghem T, Doherty A, Baczyk D, Drewlo S, Baud D, Carvalho J et al. Apelin in Normal Pregnancy and Pregnancies Complicated by Placental Insufficiency. Reprod Sci. 2016;23(8):1037-43.
Mesmin C, Fenaille F, Becher F, , Tabet JC, Ezan E. Identification and characterization of apelin peptides in bovine colostrum and milk by liquid chromatography-mass spectrometry.J Proteome Res. 2011;10(11):5222-31.
Hashimoto T, Kihara M, Ishida J, Imai N, Yoshida S, Toya Y. Apelin stimulates myosin light chain phosphorylation in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2006;26(6):1267-72.
Wang C, Du JF, Wu F, Wang HC. Apelin decreases the SR Ca2+ content but enhances the amplitude of [Ca2+]i transient and contractions during twitches in isolated rat cardiac myocytes. Am J Physiol Heart Circ Physiol. 2008;294(6):H2540-6.
Choe W1, Albright A, Sulcove J, Jaffer S, Hesselgesser J, Lavi E et al. Functional expression of the seven-transmembrane HIV-1 co-receptor APJ in neural cells. J Neurovirol. 2000;6(1):S61-9.
Fukushima H1, Kobayashi N, Takeshima H, Koguchi W, Ishimitsu T. Effects of olmesartan on Apelin/APJ and Akt/endothelial nitric oxide synthase pathway in Dahl rats with end-stage heart failure. J Cardiovasc Pharmacol. 2010;55(1):83-8.

References

Reference

Tatemoto K, Fujii R, Fujino M, Fujii R, Kakegawa T, Zou MX et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 1998; 251: 471–6.

Shin K, Chapman NA, Sarker M, Kenward C, Huang SK, Weatherbee-Martin N et al. Bioactivity of the putative apelin proprotein expands the repertoire of apelin receptor ligands. Biochim Biophys Acta. 2017 S0304-4165(17)30169-1. doi: 10.1016/j.bbagen.2017.05.017.

Medhurst AD, Davis RP, Ellis C, Davis RP, Ellis C, Winborn KY et al. Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin. J Neurochem 2003; 84 (5): 1162-72.

Kleinz MJ, Davenport AP. Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Regul Pept 2004; 118(3): 119-25.

De Falco M, Artigiano F, Cavallotti I, Cavallotti I, Artigiano F, Esposito V et al. Apelin expression in normal human tissues. In Vivo 2002; 16: 333–336.

Ferrante C, Orlando G, Recinella L, Leone S, Chiavaroli A, Di Nisio C et al. Central apelin-13 administration modulates hypothalamic control of feeding. J Biol Regul Homeost Agents. 2016; 30(3):883-88.

Rak A, Drwal E, Rame C, Knapczyk-Stwora K, SÅ‚omczyÅ„ska M, Dupont J et al. Expression of apelin and apelin receptor (APJ) in porcine ovarian follicles and in vitro effect of apelin on steroidogenesis and proliferation through APJ activation and different signaling pathways. Theriogenology. 2017; 96:126-35.

Cobellis L, De Falco M, Mastrogiacomo A, Colacurci N, De Luca A et al. Modulation of apelin and APJ receptor in normal and preeclampsia-complicated placentas. Histol Histopathol 2007; 22: 1-8.

Habata Y, Fujii R, Fujino M, Fukusumi S, Kawamata Y, Hinuma S et al. Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum. Biochim Biophys Act. 1999; 1452: 25-35.

Malamitsi-Puchner A, Gourgiotis D, Boutsikou M, Baka S, Hassiakos D, Briana DD. Circulating apelin concentrations in mother/infant pairs at term. Acta Paediatr 2007; 96: 1751-4.

Meng J, Casey PJ. Signaling through Gz. Handbook of cell signaling, edited by Bradshaw RA and Dennis EA. Boston, MA: Academic, 2004:601-604.

Challis JRG1, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev. 2000;21(5):514-50.

Liu QF, Yu HW, Sun LL, You L, Tao GZ, Qu BZ. Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and ć°NTRACELLULAR signaling pathways. Biochem Biophys Res Commun. 2015 ;468(4):617-21.

Adebiyi A, Adaikan PG, Prasad RN. Effect of benzyl isothiocyanate on spontaneous and induced force of rat uterine contraction. Pharmacol Res. 2004; 49: 415-22.

Shmygol A, Gullam J, Blanks A, Thornton S. Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility. Acta Pharmacol Sin 2006; 27: 827-32.

Kawarabayashi T, Tsukamoto T, Shojo H, Nakamura S, Sugimori H. Changes in responsiveness of freshly isolated longitudinal muscle cells from rat uterus towards oxytocin during gestation: contractility and calcium signaling. Mol Cell Endocrinol. 1997; 128: 77-84.

Van Mieghem T1, van Bree R, Van Herck E, at al. Maternal apelin physiology during rat pregnancy: the role of the placenta. Placenta. 2010;31(8):725-30.

Telejko B, Kuzmicki M, Wawrusiewicz-Kurylonek N, Szamatowicz J, Nikolajuk A, Zonenberg A, et al. Plasma apelin levels and apelin/APJ mRNA expression in patients with gestational diabetes mellitus. Diabetes Res Clin Pract. 2010; 87: 176-83.

Kourtis A, Gkiomisi A, Mouzaki M, Makedou K, Anastasilakis AD, Toulis KA, et, al. Apelin levels in normal pregnancy. Clin Endocrinol Ox. 2011; 3: 367-71

Van Mieghem T, Doherty A, Baczyk D, Drewlo S, Baud D, Carvalho J et al. Apelin in Normal Pregnancy and Pregnancies Complicated by Placental Insufficiency. Reprod Sci. 2016;23(8):1037-43.

Mesmin C, Fenaille F, Becher F, , Tabet JC, Ezan E. Identification and characterization of apelin peptides in bovine colostrum and milk by liquid chromatography-mass spectrometry.J Proteome Res. 2011;10(11):5222-31.

Hashimoto T, Kihara M, Ishida J, Imai N, Yoshida S, Toya Y. Apelin stimulates myosin light chain phosphorylation in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2006;26(6):1267-72.

Wang C, Du JF, Wu F, Wang HC. Apelin decreases the SR Ca2+ content but enhances the amplitude of [Ca2+]i transient and contractions during twitches in isolated rat cardiac myocytes. Am J Physiol Heart Circ Physiol. 2008;294(6):H2540-6.

Choe W1, Albright A, Sulcove J, Jaffer S, Hesselgesser J, Lavi E et al. Functional expression of the seven-transmembrane HIV-1 co-receptor APJ in neural cells. J Neurovirol. 2000;6(1):S61-9.

Fukushima H1, Kobayashi N, Takeshima H, Koguchi W, Ishimitsu T. Effects of olmesartan on Apelin/APJ and Akt/endothelial nitric oxide synthase pathway in Dahl rats with end-stage heart failure. J Cardiovasc Pharmacol. 2010;55(1):83-8.

Author biographies is not available.