Burt, Richard Paul;
(1996)
[alpha]1-adrenoceptor subtypes in the rat isolated epididymal vas deferens, spleen and human prostate and their signal transduction mechanisms.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The aims of this investigation were (1) to functionally characterize the [alpha]1-adrenoceptor mediating contractions of the rat isolated epididymal vas deferens, spleen and human prostate using [alpha]1-adrenoceptor subtype selective antagonists, and (2) to study the possible mechanisms of contraction to [alpha]1-adrenoceptor stimulation in these tissues. Contractions mediated by [alpha]1-adrenoceptors in the rat epididymal vas deferens and human prostate were antagonized by subtype selective competitive antagonists with pA2 values consistent with their affinities in binding studies on tissue [alpha]1A-adrenoceptors and correlated best with the antagonists published affinities for the expressed [alpha]1a-adrenoceptor clone. For the rat spleen [alpha]1-adrenoceptor mediated contractions the antagonist pA2 values were consistent with their affinities in binding studies on tissue [alpha]1B-adrenoceptors and correlated best with the antagonists published affinities for the expressed [alpha]1-adrenoceptor clone. It was concluded that the functional [alpha]1-adrenoceptor in the rat epididymal vas deferens and human prostate was the [alpha]1A-subtype and this is the same as the expressed [alpha]1a-clone, while in the rat spleen it was the [alpha]1B-subtype and this is the same as the expressed [alpha]1b-clone. The [alpha]1A-adrenoceptor mediated contraction of the rat epididymal vas deferens appeared to depend upon activation of protein kinase C by diacylglycerol, resulting in the influx of extracellular Ca2+ through voltage-gated Ca2+ channels. The [alpha]1B-adrenoceptor mediated contraction of the rat spleen consisted of an initial phasic contraction due to release of intracellular Ca2+ and a larger tonic contraction due to capacitative Ca2+ influx through non-voltage-gated Ca2+ channels and which may involve a tyrosine kinase. The [alpha]1A-adrenoceptor mediated contraction in the human prostate was dependent on both influx of extracellular Ca2+ through a partially nifedipine sensitive channel and a component which may possibly be due to either release of Ca2+ from ryanodine sensitive intracellular stores or a Ca2+ independent mechanism.
Type: | Thesis (Doctoral) |
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Qualification: | Ph.D |
Title: | [alpha]1-adrenoceptor subtypes in the rat isolated epididymal vas deferens, spleen and human prostate and their signal transduction mechanisms |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Additional information: | Thesis digitised by ProQuest. |
Keywords: | Biological sciences |
URI: | https://discovery.ucl.ac.uk/id/eprint/10099779 |
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