Insights into alpha1 adrenoceptor function in health and disease from transgenic animal studies.
Alpha(1)-adrenoceptors (ARs) mediate some of the main actions of the natural catecholamines, epinephrine and norepinephrine, and have a crucial role in the regulation of arterial blood pressure. Since alpha(1)-AR was subdivided into three subtypes (alpha(1A)-AR, alpha(1B)-AR and alpha(1D)-AR), the search has been on to discover subtype-specific physiological roles and to develop subtype-selective agonists and antagonists. Recently, several strains of genetically engineered mice have become available. Studies with these mice have provided several clues to help elucidate subtype-specific physiological functions; for instance, alpha(1A)-AR and alpha(1D)-AR subtypes play an important role in the regulation of blood pressure, suggesting that subtype-selective antagonists might be desirable antihypertensive agents. 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 pharmacological 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 Research Institute for Child Health and Development, Tokyo, Japan.
Koshimizu
Taka-aki
TA
Shibata
Katsushi
K
Nasa
Yoshihisa
Y
Takeo
Satoshi
S
Tsujimoto
Gozoh
G
D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D002490:Central Nervous System / Q000502:physiology; D002493:Central Nervous System Diseases / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000235:genetics / Q000502:physiology*; D014655:Vascular Resistance / Q000235:genetics
D018340:Receptors, Adrenergic, alpha-1