The elusive alpha(1D)-adrenoceptor: molecular and cellular characteristics and integrative roles.
alpha(1)-Adrenoceptors seem to play key roles in cardiovascular, genitourinary, and central nervous system functions. This review will be focused on alpha(1D)-adrenoceptors. These receptors have intrinsic activity, and many of the more commonly used antagonists are in reality inverse agonists. alpha(1D)-Adrenoceptors are phosphorylated in the basal state, and the natural agonists, adrenaline and noradrenaline, increase their phosphorylation; similar effects are induced by direct activation of protein kinase C and through activation of nonadrenergic receptors. Interestingly, a large proportion of alpha(1D)-adrenoceptors are located in intracellular vesicles. Such intracellular location can be changed to surface expression through the use of inverse agonists and coexpression of alpha(1B)-adrenoceptors, which seem to act as pharmacological chaperons for proper plasma membrane insertion. The alpha(1D)-adrenoceptor amino terminus seems to contain a signal that keeps the receptor intracellularly, but interaction with other proteins may also contribute. The precise relationship between the intrinsic activity, phosphorylation, and intracellular location is currently unknown. alpha(1D)-Adrenoceptor activation induces contraction in a variety of vessels, and a role in the control of blood pressure has been suggested. Studies using young prehypertensive and adult spontaneously hypertensive rats as well as knockout mice suggest that vascular alpha(1D)-adrenoceptors are involved in the genesis/maintenance of hypertension.
García-Sáinz
J Adolfo
JA
Departamento de Biología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-248, 04510, México D. F., México. agarcia@ifc.unam.mx
Villalobos-Molina
Rafael
R
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001808:Blood Vessels / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D011493:Protein Kinase C / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
C547719:ADRA1D protein, human; C547720:Adra1d protein, mouse; D058668:Adrenergic alpha-1 Receptor Antagonists; D000959:Antihypertensive Agents; D018340:Receptors, Adrenergic, alpha-1; D011493:Protein Kinase C