Transgenic studies of alpha(1)-adrenergic receptor subtype function.
Mice with altered alpha(1)-adrenergic receptor (AR) genes have become important tools in elucidating the subtype-specific functions of the three alpha(1)-AR subtypes because of the lack of sufficiently subtype-selective pharmacological agents. Mice with a deletion (knockout, KO) or an overexpression (transgenic, TG) of the alpha(1A)-, alpha(1B)-, or alpha(1D)-AR subtypes have been generated. The alpha(1)-ARs are the principal mediators of the hypertensive response to alpha(1)-agonists in the cardiovascular system. Studies with these mice indicate that alpha(1A)-AR and alpha(1B)-AR subtypes play an important role in cardiac development and/or function as well as in blood pressure (BP) response to alpha(1)-agonists via vasoconstriction. The alpha(1B)- and alpha(1D)-subtypes also appear to be involved in central nervous system (CNS) processes such as nociceptive responses, modulation of memory consolidation and working memory. The ability to study subtype-specific functions in different mouse strains by altering the same alpha(1)-AR 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 alpha(1)-AR subtypes.
Tanoue
Akito
A
Department of Molecular, Cell Pharmacology, National Center for Child Health and Development Research Institute, Tokyo, Japan.
Koshimizu
Taka-aki
TA
Tsujimoto
Gozoh
G
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002490:Central Nervous System / Q000502:physiology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008822:Mice, Transgenic; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000235:genetics*; D014655:Vascular Resistance / Q000235:genetics
D018340:Receptors, Adrenergic, alpha-1