Vasoconstrictor 5-HT receptors in the smooth muscle of the rat middle cerebral artery

Kovács, Anikó; Hársing, László G.; Szénási, Gábor

doi:10.1016/j.ejphar.2012.05.031

Cited by 14 publications

(8 citation statements)

References 43 publications

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“…However, the contractile effect of 5‐HT was also inhibited by the selective 5‐HT 1B/1D receptor blocker GR55562, albeit not as effectively as by ketanserin. 5‐HT 1B/1D receptors in smooth muscles cells have been reported to mediate vasoconstriction in rat cerebral artery (Kovacs, Harsing, & Szenasi, 2012), bovine pulmonary artery (McKenzie, Alapati, Macdonald, & Shaw, 2010), rabbit renal artery (Hill, Dora, Hughes, & Garland, 2000) and guinea pig iliac artery (Jahnichen, Radtke, & Pertz, 2004). This suggests that 5‐HT 1B/1D receptor stimulation also contributes to the 5‐HT‐evoked tone in mouse mesenteric arteries, possibly through ROK‐mediated Ca 2+ ‐sensitization mechanisms (Nuno, Korovkina, England, & Lamping, 2007).…”

Section: Discussionmentioning

confidence: 99%

Deletion of murine slc29a4 modifies vascular responses to adenosine and 5‐hydroxytryptamine in a sexually dimorphic manner

et al. 2020

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Equilibrative nucleoside transporter 4 (ENT4), encoded by SLC29A4, mediates the flux of both 5‐hydroxytryptamine (5‐HT) and adenosine across cell membranes. We hypothesized that loss of ENT4 function in mice would modify the effects of these established regulators of vascular function. Male and female wild‐type (WT) and slc29a4‐null (ENT4‐KO) mice were compared with respect to their hemodynamics and mesenteric vascular function. Male ENT4‐KO mice had a complete loss of myogenic tone in their mesenteric resistance arteries. This was accompanied by a decrease in blood flow in the superior mesenteric artery in the male ENT4‐KO mice, and a reduced responsiveness to 5‐HT. In contrast, endothelium‐dependent relaxations of mesenteric arteries from female ENT4‐KO mice were more sensitive to Ca2+‐activated K+ (KCa) channel blockade than WT mice. Female ENT4‐KO mice also demonstrated an enhanced vasodilatory response to adenosine in vivo that was not seen in males. Ketanserin (5‐HT2A inhibitor) and GR55562 (5‐HT1B/1D inhibitor) decreased 5‐HT‐induced tone, but only ketanserin inhibited the relaxant effect of 5‐HT in mesenteric arteries. 5‐HT‐evoked increases in tone were elevated in arteries from ENT4‐KO mice upon block of endothelial relaxant pathways, with arteries from female ENT4‐KO mice showing the greatest increase. Adenosine A2b receptor expression was decreased, while other adenosine transporter subtypes, as well as adenosine deaminase and adenosine kinase were increased in mesenteric arteries from male, but not female, ENT4‐KO mice. These findings indicate that deletion of slc29a4 leads to sex‐specific changes in vascular function with significant consequences for regulation of blood flow and pressure by adenosine and 5‐HT.

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Section: Discussionmentioning

confidence: 99%

Deletion of murine slc29a4 modifies vascular responses to adenosine and 5‐hydroxytryptamine in a sexually dimorphic manner

et al. 2020

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“…Blockade of 5HT2a receptors on smooth-muscle cells of brain arteries has been shown to induce relative vasodilation in animal models (i.e. blocking vasoconstriction caused by the endogenous ligand serotonin) (Kovács et al, 2012). Therefore, the degree to which these non-neuronal effects contribute to the associations described here is not known.…”

Section: Limitationsmentioning

confidence: 91%

Increased Cerebral Blood Flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

Selvaggi

Hawkins

Dipasquale

et al. 2018

Preprint

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As a result of neuro-vascular coupling, the functional effects of antipsychotics in human brain have been investigated in both healthy and clinical populations using haemodynamic markers such as regional Cerebral Blood Flow (rCBF). However, the relationship between observed haemodynamic effects and the pharmacological action of these drugs has not been fully established. Here, we analysed MRI-based rCBF data from a placebo-controlled study in healthy volunteers, who received a single dose of three different D2 receptor antagonists and tested the association of the main effects of the drugs on rCBF against normative population maps of D 2 R protein density and gene-expression data. In particular, we correlated CBF changes after antipsychotic administration with non-displaceable binding potential (BP ND ) template maps of the high affinity D 2 -antagonist Positron Emission Tomography (PET) ligand [ 18 F]Fallypride and brain post-mortem microarray mRNA expression data for the DRD2 gene. For all antipsychotics, rCBF changes were directly proportional to brain D 2 R densities and DRD2 mRNA expression measures, although PET BP ND spatial profiles explained more variance as compared with mRNA profiles (PET R 2 range= 0.20-0.60, mRNA PET R 2 range 0.04-0.20, pairwise-comparisons all p<0.05). In addition, the spatial coupling between ∆CBF and D 2 R profiles varied between the different antipsychotics tested, possibly reflecting differential affinities. Overall, these results indicate that the functional effects of antipsychotics as measured with rCBF are tightly correlated with the distribution of their target receptors in striatal and extra-striatal regions. Our results further demonstrate the link between neurotransmitter targets and haemodynamic changes reinforcing rCBF as a robust in-vivo marker of drug effects. This work is important in bridging the gap between pharmacokinetic and pharmacodynamics of novel and existing compounds.

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Section: Limitationsmentioning

confidence: 99%

Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

et al. 2019

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Vasoconstrictor 5-HT receptors in the smooth muscle of the rat middle cerebral artery

Cited by 14 publications

References 43 publications

Deletion of murine slc29a4 modifies vascular responses to adenosine and 5‐hydroxytryptamine in a sexually dimorphic manner

Deletion of murine slc29a4 modifies vascular responses to adenosine and 5‐hydroxytryptamine in a sexually dimorphic manner

Increased Cerebral Blood Flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

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