We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Agonist-specific coupling of a cloned human α<sub>1A</sub>-adrenoceptor to different second messenger pathways.
- Authors
Richardson, Joanna; Chatwin, Heather; Hirasawa, Akira; Tsujimoto, Gozoh; Evans, Peter D.
- Abstract
The agonist-specific coupling properties of the three cloned human α1-adrenoceptor subtypes have been compared, when expressed at similar levels in Chinese hamster ovary (CHO) cell lines, using noradrenaline and the (±)-meta- and (±)-para- structural isomers of octopamine as agonists. The α1A- and the α1B-adrenoceptor subtypes coupled to both the release of arachidonic acid and to the accumulation of inositol phosphates, whereas the α1D-adrenoceptor subtype only coupled effectively to the accumulation of inositol phosphates. The rank order of potencies of the three agonists tested was the same for all the three receptor subtypes when coupled to either signalling pathway: noradrenaline > meta-octopamine > para-octopamine. Meta-octopamine was a partial agonist of the α1A-adrenoceptor subtype when coupled to arachidonic acid release, whereas para-octopamine was a full agonist of this pathway. In contrast, meta-octopamine was a full agonist at the α1B-adrenoceptor subtype when coupled to arachidonic acid release, whereas para-octopamine was a partial agonist of this pathway. Neither meta-octopamine, nor para-octopamine acted as full agonists when coupling any of the three α1-adrenoceptor subtypes to the accumulation of inositol phosphates. Para-octopamine was only a weak partial agonist of this pathway for all three receptor subtypes. The results show that the modulation of arachidonic acid release and inositol 1,4,5-trisphosphate production occurs in both a subtype- and agonist-specific manner for the α1A-, α1B- and α1D-adrenoceptor subtypes. In addition, the α1A-adrenoceptor exhibits agonist-specific coupling (agonist trafficking) to the different second messenger pathways.
- Subjects
ARACHIDONIC acid; INOSITOL; PHOSPHOINOSITIDES; NEUROTRANSMITTERS; ADRENALINE
- Publication
Naunyn-Schmiedeberg's Archives of Pharmacology, 2003, Vol 367, Issue 4, p333
- ISSN
0028-1298
- Publication type
Article
- DOI
10.1007/s00210-003-0703-x