5-HT7 Receptor Restrains 5-HT-induced 5-HT2A Mediated Contraction in the Isolated Abdominal Vena Cava.
Animals
Aorta, Abdominal
/ drug effects
In Vitro Techniques
Male
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT2A
/ drug effects
Receptors, Serotonin
/ drug effects
Serotonin
/ pharmacology
Serotonin Antagonists
/ pharmacology
Serotonin Receptor Agonists
/ pharmacology
Vasoconstriction
/ drug effects
Vasodilation
/ drug effects
Vena Cava, Inferior
/ drug effects
Journal
Journal of cardiovascular pharmacology
ISSN: 1533-4023
Titre abrégé: J Cardiovasc Pharmacol
Pays: United States
ID NLM: 7902492
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
received:
18
03
2021
accepted:
04
05
2021
pubmed:
25
5
2021
medline:
2
2
2022
entrez:
24
5
2021
Statut:
ppublish
Résumé
Although discovered as a vasoconstrictor, 5-hydroxytryptamine (5-HT, serotonin) infused into man and rodent reduces blood pressure. This occurs primarily through activation of 5-HT7 receptors and, at least in part, venodilation. Vascular mechanisms by which this could occur include direct receptor activation leading to vasodilation and/or suppression of contractile 5-HT receptor activation. This study tests the hypothesis that the 5-HT7 receptor restrains activation of the 5-HT2A receptor. A subhypothesis is whether agonist-induced activation-independent of constitutive activity-of the 5-HT7 receptor is necessary for this restraint. The isolated abdominal aorta and vena cava from the normal male Sprague-Dawley rat was our model. Studies used real-time PCR and a pharmacological approach in the isolated tissue bath for measurement of isometric tone. Although 5-HT2A receptor mRNA expression in both aorta and vena cava was significantly larger than that of the 5-HT7 receptor mRNA, the 5-HT7/5-HT2A receptor mRNA ratio was greater in the vena cava (0.30) than in the aorta (0.067). 5-HT7 receptor antagonism by SB266970 and DR 4458 increased maximum contraction to 5-HT in the isolated vein by over 50% versus control. The 5-HT2A receptor agonists TCB-2 and NBOH were more potent in the aorta compared with 5-HT but less efficacious, serving as partial agonists. By contrast, these same three agonists caused no contraction in the vena cava isolated from the same rats up to 10 μM agonist. Antagonism of the 5-HT7 receptor by SB269970 did not increase either the potency or efficacy of TCB-2 or NBOH. These data support that the 5-HT7 receptor itself needs to be stimulated to reduce contraction and suggest there is little constitutive activity of the 5-HT7 receptor in the isolate abdominal vena cava.
Identifiants
pubmed: 34029269
doi: 10.1097/FJC.0000000000001057
pii: 00005344-900000000-98226
pmc: PMC8460595
mid: NIHMS1703518
doi:
Substances chimiques
Receptor, Serotonin, 5-HT2A
0
Receptors, Serotonin
0
Serotonin Antagonists
0
Serotonin Receptor Agonists
0
serotonin 7 receptor
0
Serotonin
333DO1RDJY
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
319-327Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL151413
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Acta Pharmacol Sin. 2019 Sep;40(9):1157-1167
pubmed: 30833707
Psychopharmacology (Berl). 2005 May;179(2):461-9
pubmed: 15821958
Circulation. 1956 Apr;13(4):524-7
pubmed: 13356407
BMC Pharmacol. 2012 May 06;12:4
pubmed: 22559843
J Pharmacol Exp Ther. 2008 Jun;325(3):1031-8
pubmed: 18305011
J Pharmacol Exp Ther. 1982 Mar;220(3):579-84
pubmed: 6977639
Front Neurosci. 2015 Jan 13;8:448
pubmed: 25628528
Eur J Pharmacol. 1995 Mar 24;276(1-2):183-90
pubmed: 7781688
J Hypertens. 1987 Oct;5(5):621-8
pubmed: 2963066
Am J Physiol Heart Circ Physiol. 2017 Sep 1;313(3):H676-H686
pubmed: 28626072
Br J Pharmacol. 1996 Mar;117(5):926-30
pubmed: 8851512
Eur J Pharmacol. 1993 Jun 24;237(2-3):207-13
pubmed: 8365451
Life Sci. 1984 Jul 30;35(5):477-86
pubmed: 6205240
Eur J Pharmacol. 2004 Jul 14;495(2-3):97-102
pubmed: 15249157
FASEB J. 2018 Feb;32(2):1059-1069
pubmed: 29079700
J Med Chem. 2006 Sep 21;49(19):5794-803
pubmed: 16970404
J Hypertens. 1989 Apr;7(4):311-5
pubmed: 2786023
J Pharmacol Exp Ther. 2017 Jun;361(3):441-453
pubmed: 28360333
Biochim Biophys Acta. 2009 Nov;1793(11):1646-55
pubmed: 19715731
J Auton Pharmacol. 1986 Sep;6(3):219-28
pubmed: 3771594
Br J Pharmacol. 2002 Mar;135(6):1563-71
pubmed: 11906971
Br J Pharmacol. 1989 May;97(1):292-300
pubmed: 2541857
FEBS Lett. 1995 Aug 21;370(3):215-21
pubmed: 7656980
Pharmacol Res Perspect. 2015 Feb;3(1):e00103
pubmed: 25692021
Eur J Pharmacol. 1995 Jul 14;280(3):335-7
pubmed: 8566103
Physiol Genomics. 2019 Jul 1;51(7):290-301
pubmed: 31125290
Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H907-12
pubmed: 10710360
J Cell Sci. 2012 May 15;125(Pt 10):2486-99
pubmed: 22357950
Physiol Genomics. 2019 Jul 1;51(7):302-310
pubmed: 31125292
Naunyn Schmiedebergs Arch Pharmacol. 1999 Apr;359(4):331-8
pubmed: 10344532
Front Pharmacol. 2016 May 03;7:116
pubmed: 27199758
Br J Pharmacol. 1996 Mar;117(6):993-4
pubmed: 8882587
Eur J Pharmacol. 2004 Oct 19;502(3):239-42
pubmed: 15476750
Front Pharmacol. 2011 Jul 29;2:44
pubmed: 21863140
Am J Med Sci. 1989 May;297(5):290-3
pubmed: 2785758
Pharmacology. 1991;42(1):15-22
pubmed: 1829234
Clin Physiol Biochem. 1990;8 Suppl 3:28-39
pubmed: 2132175
Br J Pharmacol. 1997 Jun;121(3):563-71
pubmed: 9179401
Naunyn Schmiedebergs Arch Pharmacol. 2006 Oct;374(1):31-9
pubmed: 16967291
Exp Brain Res. 2013 Oct;230(4):555-68
pubmed: 24042216
Heart Lung Circ. 2017 May;26(5):442-449
pubmed: 27746058
Circ Res. 1953 Jul;1(4):354-62
pubmed: 13059881
Inflamm Bowel Dis. 2014 Sep;20(9):1516-29
pubmed: 25072499
Br J Pharmacol. 1992 Oct;107(2):591-6
pubmed: 1422600
Life Sci. 1984 Mar 19;34(12):1135-41
pubmed: 6708721
Br J Pharmacol. 1992 Jul;106(3):703-9
pubmed: 1504754
Brain Res Bull. 2001 Nov 15;56(5):413-24
pubmed: 11750787
Br J Pharmacol. 1981 Feb;72(2):233-7
pubmed: 7214093
J Neurochem. 2003 Oct;87(1):22-9
pubmed: 12969249
Pharmacol Rev. 2012 Apr;64(2):359-88
pubmed: 22407614
J Smooth Muscle Res. 1998 Jun;34(3):101-10
pubmed: 9972519
Front Behav Neurosci. 2014 Oct 01;8:306
pubmed: 25324743
Br J Pharmacol. 1995 Jan;114(2):400-4
pubmed: 7881740