Abnormal Regulation of the Sympathetic Nervous System in α2A-Adrenergic Receptor Knockout Mice

摘要: α2-Adrenergic receptors (ARs) play a key role in regulating neurotransmitter release the central and peripheral sympathetic nervous systems. To date, three subtypes of α2-ARs have been cloned (α2A, α2B, α2C). Here we describe physiological consequences disrupting gene for α2A-AR. Mice lacking functional α2Asubtypes were compared with wild-type (WT) mice, animals α2B or α2C subtypes, mice carrying point mutation α2A-AR (α2AD79N). Deletion α2A subtype led to an increase activity resting tachycardia (knockout, 581 ± 21 min−1; WT, 395 min−1), depletion cardiac tissue norepinephrine concentration 676 31 pg/mg protein; 1178 98 protein), down-regulation β-ARs (Bmax: knockout, 23 1 fmol/mg 2 protein). The hypotensive effect α2 agonists was completely absent α2A-deficient mice. Presynaptic α2-AR function tested two isolated vas deferens preparations. nonsubtype-selective agonist dexmedetomidine blocked contractile response electrical stimulation from α2B-AR α2C-AR α2AD79N mutant, WT maximal inhibition contraction by knockout only 42 9%. [3H]Norepinephrine studies performed confirmed these findings. results indicate that is major presynaptic receptor nerves; however, residual α2-mediated suggests second (α2B α2C) also functions as autoreceptor inhibit transmitter release.