Regulation of Human Umbilical Artery Contractility By Different Serotonin and Histamine Receptors

Santos-Silva, António José; Cairrão, Elisa; Marques, Bruno V D; Verde, Ignácio

doi:10.1177/1933719109343787

Cited by 31 publications

(26 citation statements)

References 44 publications

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“…Fittingly, none of the groups presented in this study happened to show a significant impact on normalized cochlear blood flow. However, it has also been shown that betahistine has a direct effect on vessels [Laurikainen et al, 1998;Santos-Silva et al, 2009]. In addition to that, a study conducted by this workgroup managed to show a significant increase of cochlear blood flow caused by the infusion of aminoethylpyridine, a product of betahistine metabolism [Bertlich et al, 2014].…”

Section: Discussionmentioning

confidence: 95%

Histaminergic H<sub>3</sub>-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow

et al. 2015

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Objective: Betahistine is a histamine-like drug that is considered beneficial in Ménière's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H1-receptor and as an inverse agonist at the H3-receptor, these receptors as well as the adrenergic α2-receptor were investigated for betahistine effects on cochlear blood flow. Materials and Methods: A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H1-, H3- or α2-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. Results: Blockage of the H3- or α2-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H3-receptors caused a drop in cochlear blood flow and blood pressure. H1-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. Conclusion: Betahistine most likely affects cochlear blood flow through histaminergic H3-heteroreceptors.

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Section: Discussionmentioning

confidence: 95%

Histaminergic H<sub>3</sub>-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow

et al. 2015

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“…In the case of His, the contraction is achieved by the activation of the H 1 receptors, which is coupled to a Gq protein, that activates the PLC/IP 3 signaling cascade, leading to an intracellular increase of Ca 2+ …”

Section: Physiological Regulation Of Hua Contractilitymentioning

confidence: 99%

“…However, the HUA smooth muscle also expresses another 5‐HT receptor (5‐HT 7 ) and two other receptors of His (H 2 and H 3 ) that are associated with a Gs protein. The activation of these receptors stimulates adenyl cyclase and leads to vasorelaxation …”

Section: Physiological Regulation Of Hua Contractilitymentioning

confidence: 99%

“…35 Its contractile effects are due to the activation of 5-HT 2A receptors and partially due to the activation of 5-HT 1B /5-HT 1D receptors. 46 The 5-HT 2A receptor is coupled to the Gq protein and activates PLC, resulting in an increase of inositol IP 3 levels. [46][47][48][49][50] On the other hand, the 5-HT 1B and 5-HT 1D receptors are coupled to the Gi/o protein inhibiting adenyl cyclase.…”

Section: Contraction Of Smc From Huamentioning

confidence: 99%

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How is the human umbilical artery regulated?

Lorigo

Mariana

Feiteiro

2018

J of Obstet and Gynaecol

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The purpose of this review is to present an update of the main mechanisms involved in the physiological regulation of contraction and relaxation of the human umbilical artery (HUA) smooth muscle cells. A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the regulation of the HUA are presented in this article. The vascular smooth muscle is a highly specialized structure, whose main function is to regulate the vascular tonus. This is controlled by a balance between the cellular signaling pathways that mediate contraction and relaxation. The cells responsible for the contractile property of this muscle are the smooth muscle cells (SMC), and an excellent source of these cells is the HUA, involved in fetoplacental circulation. Since the umbilical blood vessels are not innervated, the HUA tonus is modulated by vasoactive substances that regulate the contractile process. The main vasoactive substances that induce contraction are serotonin, histamine, thromboxane, bradykinin, endothelin 1 and prostaglandin F2α, that are linked to the activation of proteins G and G . On the other hand, the main vasorelaxation mechanisms are the activation of adenyl and guanil cyclases, potassium channels and the inhibition of calcium channels. The SMC from the HUA allow the study of different cellular mechanisms and their functions. Therefore, these cells are an important tool to study the mechanisms regulating the contractility of this artery, allowing to detect potential therapeutic targets to treat HUA disorders (gestational hypertension and pre-eclampsia).

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“…SSRIs, and some other antidepressants, act on the crucial serotonin transporter (SERT, aka 5HTT, SLC6A4, OMIM 182138), which regulates the synaptic concentration of serotonin (5HT) in many tissues, including the placenta[7]. The resultant increased bioavailability of serotonin affects vasoconstriction and coagulation or bruising [6,8,9], cardiac morphogenesis [10,11], CNS development[6] gastrulation, laterality and craniofacial development[10], conferring biological plausibility on reported associations between SSRI exposure during organogenesis and certain congenital anomalies.…”

Section: Introductionmentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

et al. 2016

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BackgroundHypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP).Methods and FindingsThree population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression.ConclusionThe additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care.

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Regulation of Human Umbilical Artery Contractility By Different Serotonin and Histamine Receptors

Cited by 31 publications

References 44 publications

Histaminergic H<sub>3</sub>-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow

Histaminergic H<sub>3</sub>-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow

How is the human umbilical artery regulated?

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

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