Serotonergic mechanisms of regulation of the systemic circulation vessels lumen

Abstract

Review is devoted to the assessment of the serotonergic mechanisms role in the hemodynamics regulation. The special attention is given to the role of various serotonin receptors involved in the gastrointestinal tract motility regulation, in particular located in the digestive system vessel walls. It is known that serotonin has a dual effect on the vessel lumen, due to the heterogeneity of serotonin receptors, which are part of the vascular wall, and different sensitivity of serotonin receptors. Mechanisms at various levels, from central to local, are able to participate in the serotonergic regulation of the vascular lumen, as well as in motility control. According to our data, in the regulation of the upper gastrointestinal tract motor activity participate 5-HT1B- and 5-HT3-receptors located in the stomach and intestines autonomic ganglia, 5-HT2B-receptors localized on stomach plexus neurons and on small and large intestine smooth muscles; 5-HT4-receptors located on stomach wall smooth muscles and intraorgan intestinal plexus neurons. According to the literature, vascular wall 5-HT2B- and 5-HT7-receptors provide vasodilation, whereas the 5-HT1B/1D-, 5-HT2A- and 5-HT2B-receptors - vasoconstriction. Significance of plasma free serotonin level for hemodynamic, serotonergic mechanisms for the different types vessels diameter changing, the interaction of serotonin receptors with sympathetic nervous system and their possible role in the vascular tone regulation are described, particularly the role of presynaptic 5-HT1B/1D-receptors, which prevent the catecholamines release by vegetative nerves endings, is established. Different points of view on the serotoninergic regulation issue, existing contradictions, as well as areas for further fundamental and practical research are presented.

Keywords

serotonin / visceral circulation / 5-HT-receptors / regulation / mechanisms

References

[1] Ахметзянов В.Ф., Латфуллин И.А., Нигматуллина Р.Р. Современные представления о роли серотонинергической системы в регуляции сердечно-сосудистой деятельности в норме и патологии. Казанский мед. ж. 2006; 87 (2): 110-121.

[2] Нигматуллина Р.Р., Кириллова В.В., Джорджикия Р.К. и др. Концентрация серотонина в крови и тромбоцитах у пациентов с ХСН. Ж. сердечн. недостат. 2008; 9 (6): 289-291.

[3] Свешников Д.С., Смирнов В.М., Мясников И.Л., Кучук А.В. Исследование природы нервных волокон симпатического ствола, вызывающих усиление сокращений желудка. Бюлл. эксперим. биол. и мед. 2011; 152 (9): 249-252.

[4] Свешников Д.С., Торшин В.И., Смирнов В.М. и др. Значение различных серотониновых рецепторов в регуляции моторики желудочно-кишечного тракта. Патол. физиол. и эксперим. терап. 2014; (3): 45-51.

[5] Barnes N., Andrade R., Bockaert J. et al. 5-Hydroxytryptamine receptors, introduction. IUPHAR/BPS Guide to Pharmacology. Last modified on 19/11/2014. http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=1 (access date: 12.06.2015).

[6] Bhaskaran S., Zaluski J., Banes-Berceli A. Molecular interactions of serotonin (5-HT) and endothelin-1 in vascular smooth muscle cells: in vitro and ex vivo analyses. Am. J. Physiol. Cell Physiol. 2014; 306 (2): 143-151. http://dx.doi.org/10.1152/ajpcell.00247.2013

[7] Brenner B., Harney J.T., Ahmed B.A. et al. Plasma serotonin levels and the platelet serotonin transporter. J. Neurochem. 2007; (102): 206-215. http://dx.doi.org/10.1111/j.1471-4159.2007.04542.x

[8] Centurion D., Glusa E., Sanchez-Lopez A. et al. 5-HT7, but not 5-HT2B, receptors mediate hypotension in vagosympathetctomized rats. Eur. J. Pharmacol. 2004; (502): 239-242. http://dx.doi.org/10.1016/j.ejphar.2004.08.050

[9] Cohen M.L., Fuller R.W., Kurz K.D. LY53857, a selective and potent serotonergic (5-HT2) receptor antagonist, does not lower blood pressure in the spontaneously hypertensive rat. J. Pharmacol. Exp. Ther. 1983; (227): 327-332.

[10] Dalton D.W., Feniuk W., Humphrey P.P. An investigation into the mechanisms of the cardiovascular effects of 5-hydroxytryptamine in conscious normotensive and DOCA-salt hypertensive rats. J. Auton. Pharmacol. 1996; (6): 219-228.

[11] Darios E.S., Barman S.M., Orer H.S. et al. 5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation. Eur. J. Pharmacol. 2015; (5): 140-147. http://dx.doi.org/10.1016/j.ejphar.2015.02.032

[12] Diaz J., Ni W., King A. et al. 5-Hydroxytryptamine lowers blood pressure in normotensive and hypertensive rats. J. Pharmacol. Exp. Ther. 2008; (325): 1031-1038. http://dx.doi.org/10.1124/jpet.108.136226

[13] Dong J.S., Hyun J.N., Jae G.K. et al. Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase. Experim. Mol. Med. 2013; (45): 1-10.

[14] Dorn S.D., Morris C.B., Hu Y. Irritable bowel syndrome subtypes defined by Rome II and Rome III criteria are similar. J. Clin. Gastroenterol. 2009; (43): 214-220. http://dx.doi.org/10.1097/MCG.0b013e31815bd749

[15] Gaddum J.H., Picarelli Z.P. Two kinds of tryptamine receptor. Br. J. Pharmacol. 1957; (12): 323-328. http://dx.doi.org/10.1111/j.1476-5381.1957.tb00142.x

[16] Gershon M.D. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr. Opin. Endocrinol. Diabetes Obes. 2013; 20 (1): 14-21. http://dx.doi.org/10.1097/MED.0b013e32835bc703

[17] Gershon M.D., Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007; 132 (1): 397-414. http://dx.doi.org/10.1053/j.gastro.2006.11.002

[18] Gothert M., Molderings G.J., Fink K., Schlicker E. Heterogeneity of presynaptic serotonin receptors on sympathetic neurons in blood vessels. Blood Vessels. 1991; (28): 11-18.

[19] Gradin K., Pettersson A., Hedner T., Persson B. Chronic 5-HT2 receptor blockade with ritanserin does not reduce blood pressure in the spontaneously hypertensive rat. J. Neural. Transm. 1985; (64): 145-149. http://dx.doi.org/10.1007/BF01245975

[20] Kawasaki H., Takasaki K. Vasoconstrictor response induced by 5-hydroxytryptamine released from vascular adrenergic nerves by periarterial nerve stimulation. J. Pharmacol. Exp. Ther. 1984; (229): 816-822. http://dx.doi.org/10.1111/j.1440-1681.2011.05504.x

[21] Linder A.E., Davis R.P., Burnett R., Watts S. Function of the serotonin transporter in vasculature of the female rat: comparison with the male. Clin. Exp. Pharmacol. Physiol. 2011; 38 (5): 314-322.

[22] Machida T., Iizuka K., Hirafuji M. Recent advances in 5-hydroxytryptamine (5-HT) receptor research: how many pathophysiological roles does 5-HT play via its multiple receptor subtypes? Biol. Pharm. Bull. 2013; 36 (9): 1416-1419. http://dx.doi.org/10.1248/bpb.b13-00344

[23] Moreno L., Martinez-Cuesta M.A., Pique J.M. et. al. Anatomical differences in responsiveness to vasoconstrictors in the mesenteric veins from normal and portal hypertensive rats. Naunyn Schmiedebergs Arch. Pharmacol. 1996; (354): 474-480. http://dx.doi.org/10.1007/BF00168439

[24] Ni W., Geddes T.J., Priestley J.R. et al. The existence of a local 5-hydroxytryptaminergic system in peripheral arteries. Br. J. Pharmacol. 2008; (154): 663-674. http://dx.doi.org/10.1038/bjp.2008.111

[25] Ni W., Thompson J., Northcott C. et al. The serotonin transporter is present and functional in peripheral arterial smooth muscle. J. Cardiovasc. Pharmacol. 2004; (43): 770-781. http://dx.doi.org/10.1097/00005344-200406000-00006

[26] Russell A., Banes A., Berlin H. et al. 5-Hydroxytryptamine 2B receptor function is enhanced in the N-nitro-L-arginine hypertensive rat. J. Pharmacol. Exp. Ther. 2002; (303): 179-187. http://dx.doi.org/10.1124/jpet.102.037390

[27] Terron J.A., Sanchez-Maldonado C., Martinez-Garcia E. Pharmacological evidence that 5-HT1B/1D receptors mediate hypotension in anesthetized rats. Eur. J. Pharmacol. 2007; (576): 132-135. http://dx.doi.org/10.1016/j.ejphar.2007.08.005

[28] Van Zwieten P.A., Blauw G.F., van Brummelen P. Serotonergic receptors and drugs in hypertension. Pharmacol. Toxicol. 1992; (70): 17-22. http://dx.doi.org/10.1111/j.1600-0773.1992.tb01617.x

[29] Watts S.W., Davis R.P. 5-Hydroxtryptamine receptors in systemic hypertension: an arterial focus. Cardiovasc. Ther. 2011; 29 (1): 54-67. http://dx.doi.org/10.1111/j.1755-5922.2010.00173.x

[30] Watts S.W., Darios E.S., Seitz B.M., Thompson J.M. 5-HT is a potent relaxant in rat superior mesenteric veins. Pharmacol. Res. Perspect. 2015; 3 (1): e00103. doi: 10.1002/ prp2.103. Epub 2015 Jan. 5.

[31] Watts S.W., Baez M., Webb R.C. The 5-hydroxytryptamine 2B receptor and 5-HT receptor signal transduction in mesenteric arteries from deoxycorticosterone acetate-salt hypertension. J. Pharmacol. Exp. Ther. 1996; (277): 1103-1113.

[32] Wouters M.M., Farrugia G., Schemann M. 5-HT receptors on interstitial cells of Cajal, smooth muscle and enteric nerves. Neurogastroenterol. Motil. 2007; 19 (2): 5-12. http://dx.doi.org/10.1111/j.1365-2982.2007.00963.x

RIGHTS & PERMISSIONS

Sveshnikov D.S., Kuchuk A.V., Smirnov V.M., Cherepanova G.V.