Subclassification and nomenclature of α1- and α2-adrenoceptors

Substitution of a mutant α 2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

“…The considerably attenuated ␣ 2 ARagonist-induced inhibition of Ca 2ϩ currents in SCG neurons from mutant mice was completely suppressed by prazosin (Fig. 5F), an ␣ 1 AR antagonist that also blocks ␣ 2B AR and ␣ 2C AR subtypes (but not the ␣ 2A AR subtype) with reasonably high potency (5), suggesting that the residual voltage-gated Ca 2ϩ current response to ␣ 2 AR agonists in neurons from D79N mice is mediated by ␣ 2B and͞or ␣ 2C AR subtype. Thus, the D79N mutant ␣ 2A AR is unable to evoke inhibition of voltage-gated Ca 2ϩ currents in SCG neurons, similar to the loss of responses observed in LC neurons derived from D79N mutant mice.…”

“…Subtype-specific ␣ 2 AR agonists and antagonists are not available (5); even when subtype selectivity has been noted in vitro, varying and unknown in vivo bioavailability precludes confident correlation of the administered dose with the amount of drug at the receptor site. Previous studies to explore ␣ 2 AR involvement in various responses have used prazosin to block catecholamine responses mediated by ␣ 1 adrenergic receptors (␣ 1 AR); however, it is now known that the ␣ 2B AR and ␣ 2C AR subtypes also are blocked by prazosin (5), thus confounding the interpretations of these earlier studies.…”

“…Subtype-specific ␣ 2 AR agonists and antagonists are not available (5); even when subtype selectivity has been noted in vitro, varying and unknown in vivo bioavailability precludes confident correlation of the administered dose with the amount of drug at the receptor site. Previous studies to explore ␣ 2 AR involvement in various responses have used prazosin to block catecholamine responses mediated by ␣ 1 adrenergic receptors (␣ 1 AR); however, it is now known that the ␣ 2B AR and ␣ 2C AR subtypes also are blocked by prazosin (5), thus confounding the interpretations of these earlier studies. In addition, because ␣ 1 AR can functionally antagonize ␣ 2 AR-mediated responses in some settings, ␣ 2 AR responses in the presence of prazosin (added to block ␣ 1 AR, ␣ 2B AR, and ␣ 2C AR) may reflect the disturbance of the balance between the functionally antagonistic ␣ 2 AR and ␣ 1 AR systems rather than provide insights concerning the role of the ␣ 2A AR subtype.…”

Different Subtypes of α1-Adrenoceptor Modulate Different K+ Currents via Different Signaling Pathways in Canine Ventricular Myocytes

“…Many cellular responses to ␣ 1 ARs are mediated by multiple subtypes (␣ 1A , ␣ 1B , and ␣ 1D ) (1)(2)(3)(4). In the heart, whereas the ␣ 1A and ␣ 1B subtypes have been well characterized, the presence of ␣ 1D AdR was indicated only recently (5)(6)(7).…”

Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

“…They regulate blood pressure by changing the tonus of the vascular muscles. According to the current classification developed by the International Union of Pharmacology Subcommittee on Nomenclature for Adrenoceptors, there are three subtypes of α 1 -adrenergic receptor: α 1A , α 1B , α 1D (Hieble and Ruffolo 1996;Docherty 1998;Langer 1999).…”