Search for a mammalian homologue of a novel turkey receptor and desensitization of the turkey beta(2)-adrenergic receptor
Subsequent Statement of Responsibility
R. A. Nicholas
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
The University of North Carolina at Chapel Hill
Date of Publication, Distribution, etc.
1998
PHYSICAL DESCRIPTION
Specific Material Designation and Extent of Item
134-134 p.
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
Ph.D.
Body granting the degree
The University of North Carolina at Chapel Hill
Text preceding or following the note
1998
SUMMARY OR ABSTRACT
Text of Note
The mammalian usd\betausd-AR family has three well-characterized subtypes, the usd\beta\sb1usd-, usd\beta\sb2usd-, and usd\beta\sb3usd-adrenergic receptors. Recent cloning of a novel turkey usd\betausd-adrenergic receptor (usd\betausd-AR), called the usd\beta\sb{\rm 4c}usd-AR, has suggested the possibility of the existence of an additional mammalian usd\betausd-AR. We utilized PCR, Southern blot analysis, and library screening in an effort to clone a potential human homologue of the turkey usd\beta\sb{\rm 4c}usd-AR. Screening of two human genomic libraries resulted in the isolation of 29 clones encoding human usd\betausd-ARs: 19 usd\beta\sb1usd-AR clones, 3 usd\beta\sb2usd-AR clones, and 7 usd\beta\sb3usd-AR clones. In addition, two clones encoding the 5HT1a receptor were isolated. Since all of the known usd\betausd-AR genes were cloned by this method, but no usd\beta\sb{\rm 4c}usd-AR homologue, these studies suggest that a mammalian homologue of the turkey usd\beta\sb{\rm 4c}usd-AR does not exist. Turkeys also express a usd\beta\sb2usd-AR with 82% identity to the human usd\beta\sb2usd-AR that terminates 16 aminoacids earlier than the human usd\beta\sb2usd-AR. Furthermore, the turkey usd\beta\sb2usd-AR lacks multiple serine and threonine residues in its carboxy-terminus, suggesting a potential alteration in the desensitization properties of the turkey receptor compared to human. We expressed both turkey and human usd\beta\sb2usd-ARs in the same cell line at similar receptor densities and showed that the affinities of a series of agonists and antagonists were nearly identical at both receptors. Functionally, both turkey and human usd\beta\sb2usd-ARs couple to elevations in cellular cyclic AMP and their propensities to undergo both homologous and long-term desensitization were nearly identical. These data indicate that the desensitization properties of the turkey and human usd\beta\sb2usd-adrenergic receptors are very similar, even though the turkey usd\beta\sb2usd-AR lacks multiple phosphorylation sites.