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Effect of cocaine and desmethylimipramine on the α1-adrenoceptor mediated contractions of rat vas deferens and other isolated tissues

Varsani, Mina; (2003) Effect of cocaine and desmethylimipramine on the α1-adrenoceptor mediated contractions of rat vas deferens and other isolated tissues. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

It has been observed in the rat epididymai vas deferens that pA2 values for the α1-adrenoceptor antagonist prazosin are lower in the presence of the uptake blocker DMI than in the presence of the uptake blocker cocaine. The present aims were to investigate the effects of cocaine or DMI on the pA2 values obtained for prazosin and the α1-adrenoceptor antagonists 5-methyl urapidil, WB-4101 and phentolamine at the rat and human tissues. α1a-, α1b- and α1d-adrenoceptor mRNA were detected in each of the tissues investigated. mRNA was not detected for any other possible α1-adrenoceptor subtypes. At the rat epididymai vas deferens, pA2 values for prazosin, 5-methyl urapidil, WB-4101 and phentolamine were significantly lower in the presence of DMI than in the presence of cocaine or nisoxetine. α1-Adrenoceptor antagonist pA2 values differed in the presence of cocaine and DMI when the uptake sensitive agonist phenylephrine was used. pA2 values did not differ in the presence of cocaine or DMI when the uptake insensitive agonists methoxamine or neurokinin A were employed, suggesting the effect of DMI may involve the uptake mechanism. In the rat prostatic vas deferens and thoracic aorta, pKB values for prazosin did not differ in the presence of cocaine or DMI, suggesting the effect of DMI on α1-adrenoceptor antagonist pA2 values to be limited to the rat epididymal vas deferens in these studies. pA2 values for prazosin, 5-methyl urapidil, WB-4101 and BMY 7378 at the human internal mammary artery suggested that contractions of this tissue are mediated predominantly by the α1A-adrenoceptor subtype. pKB values obtained for prazosin did not differ in the presence of cocaine or DMI. DMI may affect α1-adrenoceptor antagonist pA2 values at the rat epididymal vas deferens by the down-regulation of noradrenaline transporters at this tissue. Further studies are required to clarify this possibility.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Effect of cocaine and desmethylimipramine on the α1-adrenoceptor mediated contractions of rat vas deferens and other isolated tissues
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10107146
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