Investigation of trace amine receptors in the cardiovascular systems

Doctoral thesis English OPEN
Fehler, Martina
  • Subject: RM
    mesheuropmc: animal structures

Trace amines (TAs), including p-phenylethylamine (p-PEA), tyramine and octopamine are structurally and functionally related to biogenic amines such as catecholamines and serotonin and to amphetamines. They are present in trace levels in the nervous system and in chocolate, cheese and wine. TAs are usually regarded as indirectly-acting sympathomimetic amines (ISAs) exerting vasoconstriction via a-adrenoceptors. However, they also stimulate trace amine-associated receptors (TAARs), of which only TAAR1 and TAAR4 are sensitive to TAs. The aim of the thesis was to examine whether vasoconstriction by TAs in blood vessels is via ISA or TA mechanisms. TAs caused concentration-related and endothelium-independent contractions in rat isolated aortic rings in the presence of prazosin (ai-adrenoceptor antagonist), cocaine (catecholamine uptake inhibitor), ICI-118,551-adrenoceptor antagonist) and pargyline (MAO A and B inhibitor). The persistent and inhibitor-independent contractions suggest that mechanisms other than ISA and a- and p- adrenoceptor stimulation are involved, possibly TAARs. Differences in the profile of vasoconstrictor activities to a range of TAs were identified in rat and guinea-pig aorta, suggesting species variations in receptor distribution. Tyramine was identified as a partial agonist in isolated rat aorta and an antagonist of other TAs in this tissue. Finally, the presence of TAAR1 mRNA and protein was demonstrated for the first time in rat aorta by RT-PCR and Western blotting, respectively. Most information about TAs relates to studies which have been done on the brain, or cloned receptors expressed in transfected cells. This study of different TAs and structurally related derivatives in aortic tissues has expanded the knowledge of the vasoconstrictor effects of TAs in isolated tissues. The molecular biological confirmation of the presence of TAAR1 and the pharmacological findings regarding the effects of TAs in rat aortic rings might explain their hypertensive effects and their role in coronary heart disease and migraine headache.
  • References (74)
    74 references, page 1 of 8

    MATERIAL AND METHODS ....................................................................... 79

    MATERIAL AND METHODS ..................................................................... 144

    7.3.2 Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)...........................................................................................236

    Chapter 8: General Discussion

    8.1 GENERAL DISCUSSION............................................................................... 253

    8.2 FUTURE W O R K ............................................................................................. 264

    8.3 GENERAL CONCLUSION ............................................................................ 265

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    O'Donnell S. R. and Wanstall J. C. (1984b) The classification of beta-

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