Abstract
Mice with altered α2-adrenergic receptor genes have become important tools in elucidating the subtype-specific functions of the three α2-adrenergic receptor subtypes because of the lack of sufficiently subtype-selective pharmacological agents. Mice with a deletion (knockout) of the α2A-, α2B-, or α2C-gene as well as a point mutation of the α2A-gene (α2A-D79N) and a 3-fold overexpression of the α2C-gene have been generated. Studies with these mice indicate that most of the classical functions mediated by the α2-adrenergic receptor, such as hypotension, sedation, analgesia, hypothermia, and anesthetic-sparing effect, are mediated primarily by the α2A-subtype. The α2B-subtype is the principal mediator of the hypertensive response to α2-agonists, appears to play a role in salt-induced hypertension, and may be important in developmental processes. The α2C-subtype appears to be involved in many central nervous system processes such as the startle reflex, stress response, and locomotion. Both the α2A- and α2C-subtypes are important in the presynaptic inhibition of norepinephrine release and appear to have distinct regulatory roles. The ability to study subtype-specific functions in different mouse strains by altering the same α2-adrenergic receptor in different ways strengthens the conclusions drawn from these studies. Although these genetic approaches have limitations, they have significantly increased our understanding of the functions of α2-adrenergic receptor subtypes.
Footnotes
-
Send reprint requests to: David B. Bylund, Ph.D., Department of Pharmacology, 986260 Nebraska Medical Center, Omaha, NE 68198-6260. E-mail: dbylund{at}unmc.edu
-
↵1 This work was supported by National Institutes of Health Grant NS33194.
-
↵2 Current address: Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104-6074.
-
Received for publication October 25, 1999.
- Abbreviations:
- KO
- knockout
- OE
- overexpression
- PPI
- prepulse inhibition
- Accepted January 3, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|