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Title: Adenosine receptors in the basilar artery of the rat
Author: Davidson, H. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1999
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Adenosine receptors that mediate vasodilatation on the rat basilar artery are determined, and the transduction mechanisms by which they mediate their relaxations investigated. Furthermore, the effect of reactive oxygen species and hypoxia upon this vessel are described. Dilatation of the rat basilar artery by adenosine receptors is a complex process involving more than one receptor. The functional data obtained using the small vessel myograph are consistent with the combined action of at least three adenosine receptors. The adenosine receptor agonist, NECA, acts upon A2 receptors in the lower concentration range (< 10 μM) of its biphasic curve whilst the higher concentration range is xanthine-insensitive, suggesting the action of the A3 receptor. R-PIA also acts upon the xanthine-insensitive receptor whilst IB-MECA and APNEA would appear to be acting via A2 receptors. Using reverse transcription with the polymerase chain reaction, all four adenosine receptors were shown to be expressed in groups of rat dissociated basilar artery myocytes. The A1 receptor is expressed but does not mediate vasodilatation. The first phase of the NECA curve mediates relaxation by positively coupling to adenylyl cyclase, shown by the blockade of relaxations in the lower concentrations range of the NECA curve by the protein kinase inhibitor Rp-cAMPS. R-PIA would appear to act upon the A3 receptor mediating relaxation, in part, via NO release as shown by shifting of the concentration-effect curve to R-PIA in the absence of endothelium and the presence of L-NAME. The second mechanism by which R-PIA mediates its relaxation was not determined but is not via potassium channels, adenylyl cyclase, release of 5-HT and histamine from mast cells nor prostanoid release. Investigation into the mRNA encoding for adenylyl cyclase isotypes revealed the presence of multiple isoforms on the rat basilar artery, namely Types II, III, IV, V, VI, VIII with a splice variant detected for Type IV.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available