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THE JANUS* FACES OF ADRENOCEPTORS: FACTORS CONTROLLING THE COUPLING OF ADRENOCEPTORS TO MULTIPLE SIGNAL TRANSDUCTION PATHWAYS
Author(s) -
Summers Roger J,
Broxton Natalie,
Hutchinson Dana S,
Evans Bronwyn A
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.04094.x
Subject(s) - agonist , receptor , signal transduction , g protein , pertussis toxin , microbiology and biotechnology , g protein coupled receptor , biology , chemistry , biochemistry
SUMMARY 1. The adrenoceptors (AR) are an important subfamily of rhodopsin‐like G‐protein‐coupled receptors that couple to an increasingly large number of signalling mechanisms. Two important factors that determine the pathways that are used are the C‐terminal region of the receptor and the agonist used to activate the receptor. 2. Studies of splice variants of the mouse β 3 ‐AR showed that the C‐terminus is a factor controlling the signalling characteristics. Although these receptors differ only at the C‐terminus, the β 3b ‐AR coupled to both G s and G i , whereas the β 3a ‐AR coupled solely to G s . 3. Examination of four splice variants of the human α 1A ‐AR showed that all were able to couple to pertussis toxin‐sensitive G‐proteins, even though they have radically different C‐terminal regions. 4. Comparison of the effects of the β 3 ‐AR ligands CL316243 and SR59230A showed that both can activate the mouse β 3 ‐AR but that SR59230A uses pathways other than cAMP accumulation in 3T3‐F442A cells. 5. Examination of a series of α 1 ‐AR agonists for their ability to activate a number of signalling pathways revealed that A61603 acted as a full agonist in all assays, whereas oxymetazoline was unable to cause cAMP accumulation, suggesting agonist‐selective signalling at the human α 1A ‐AR.