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Bitter taste recept...
Bitter taste receptor agonists mediate relaxation of human and rodent vascular smooth muscle.
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- Manson, Martijn L (författare)
- Karolinska Institutet
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- Säfholm, Jesper (författare)
- Karolinska Institutet
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- Al-Ameri, Mamdoh (författare)
- Karolinska Institutet
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- Bergman, Per (författare)
- Karolinska Institutet
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- Orre, Ann-Charlotte (författare)
- Karolinska Institutet
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- Swärd, Karl (författare)
- Lund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups
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- James, Anna (författare)
- Karolinska Institutet
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- Dahlén, Sven-Erik (författare)
- Karolinska Institutet
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- Adner, Mikael (författare)
- Karolinska Institutet,Lund University,Lunds universitet,Klinisk och experimentell allergiforskning,Laryngoesofagologi, allergi och livskvalitet,Forskargrupper vid Lunds universitet,Clinical and Experimental Allergy Research,Laryngoesophagology, Allergy and Life Quality,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- Engelska.
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 740:Jul 15, s. 302-311
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Taste-sensing type 2 receptors (TAS2Rs) have been implicated in extraoral functions. Airway smooth muscle expresses TAS2Rs and is strongly relaxed by TAS2R agonists. We hypothesised that TAS2R agonists might affect vascular smooth muscle as well. Moreover, the general pharmacological profile of TAS2R agonists, which are used to investigate the functions of TAS2R׳s, are undefined. The aim of this study was to pharmacologically characterise the effects of five prototype TAS2R agonists in vascular smooth muscle. Responses to the TAS2R agonists were investigated in guinea-pig aorta and taenia coli, mouse aorta (wild-type and caveolin-1(-/-) mice) and human pulmonary arteries. Chloroquine, denatonium, dextromethorphan, noscapine and quinine, agonists for TAS2R3, TAS2R4, TAS2R10 and TAS2R14, induced strong endothelium-independent relaxations (responses between 82-96% of maximal relaxations) in phenylephrine pre-contracted guinea-pig aorta that persisted in the presence of L-type Ca(2+) and KCa1.1-channel blockers. Experiments in guinea-pig taenia coli revealed that denatonium and quinine also inhibited relaxations to phenylephrine, indicating antagonism of α-adrenoceptors. Only chloroquine and noscapine mediated relaxations when the guinea pig aorta was pre-contracted by U-46619 or PGF2α. Relaxations to chloroquine and noscapine after U-46619 pre-contractions were however markedly impaired in aortae from caveolin-1(-/-) mice. Chloroquine and noscapine mediated relaxations of human pulmonary arteries that expressed also mRNA for TAS2R3, TAS2R4, TAS2R10 and TAS2R14, at levels similar to that of the α1A adrenoceptor. Notwithstanding whether TAS2Rs are involved or not, TAS2R agonists have profound effects on vascular smooth muscle. Chloroquine and noscapine are of special interest as their effects cannot be accounted for by conventional pathways.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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