Regional differences in α1-adrenoceptor subtypes and mechanisms in rabbit arteries

Antagonistic effects of selective α1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery

“…Partial agonists, such as clonidine and tizanidine, act as competitive antagonists toward the α 1Badrenoceptor subtype (rabbit iris dilator, pA 2 l 6.05 and 5.51, respectively), although they act as agonists toward the α 1A -adrenoceptor subtype in rabbit thoracic aorta and iliac artery (Takayanagi et al 1991 ;Satoh et al 1992a, b). The selective properties of α 1D -antagonist MDL73005EF demonstrated here support our previous findings in which we reported the co-existence of an α 1D -adrenoceptor subtype in addition to the α 1A -and α 1B -adrenoceptor subtypes in rabbit iliac artery (Satoh et al 1998(Satoh et al , 1999, and so we used partial agonists clonidine and tizanidine to characterize the α 1D -adrenoceptor subtype in rat thoracic aorta. As shown in Figures 1A and 2A and Tables 1 and 2, in rat thoracic aorta the concentration-response curves of noradrenaline were potently antagonized by MDL-73005EF and tamsulosin, and the pA 2 values for MDL-73005EF and tamsulosin were 8.30p0.04 and 10.51p 0.04, respectively.…”

“…This indicates the existence of an MDL73005EF-and tamsulosin-sensitive α 1D -adrenoceptor subtype in rabbit iliac artery and also suggests the possibility of a contractile response through this α 1D -adrenoceptor subtype for the noradrenaline-induced contractions of smooth muscle in rabbit iliac artery, as reported previously using a selective α 1D -adrenoceptor antagonist BMY 7378 (Satoh et al 1998(Satoh et al , 1999. These findings suggest that noradrenaline-induced contraction in rat thoracic aorta is predominantly mediated through the α 1Dadrenoceptor subtype, that MDL73005EF and tamsulosin have high affinity for the α 1D -adrenoceptor subtype, and that an α 1D -adrenoceptor subtype contributes to the α 1 -adrenoceptor mediation of muscle contraction in rabbit iliac artery.…”

“…The α 1D -adrenoceptor subtype plays an important role in noradrenaline-induced muscle contraction in rat aorta using the selective α 1D -adrenoceptor antagonist BMY 7378 (Saussy et al 1994 ;Kenny et al 1995). Rabbit renal and iliac artery were contracted via the activation of the α 1D -adrenoceptor subtype in addition to the α 1A -and α 1Badrenoceptor subtypes, whereas rabbit thoracic and abdominal aorta were contracted via the activation of α 1A -and α 1B -adrenoceptor subtypes using BMY 7378, WB4101 and 5-methylurapidil (Satoh et al 1998(Satoh et al , 1999. Putative α 1 -adrenoceptor antagonist MDL73005EF apparently has a sensitivity over 10-fold higher for the α 1D -adrenoceptor subtype (pK B " 8) than for α 1A -and α 1B -adrenoceptor subtypes (pK B " 7) (Hieble et al 1995).…”

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

“…However, direct binding studies showed that BMY 7378 inhibits 3 H-prazosin binding in the rabbit aorta with low affinity, presumably by binding to α 1A -and α 1B -adrenergic receptors. Moreover, relative level of expression of α 1D -adrenergic receptor mRNA in rabbit aorta is approximately 50 × lower than that of the α 1A -adrenergic receptor mRNA (Satoh et al 1998;Piao et al 2000). Negligible α 1D -adrenergic receptor function in aortic tonus regulation seems to be typical of rabbits, because administration of BMY 7378 blocked the α 1D -adrenergic receptor in the aorta of rats, leading to its dilatation (Goetz et al 1995).…”

Differences of Antagonism for a Selective .ALPHA.1D-Adrenoceptor Antagonist BMY 7378 in the Rabbit Thoracic Aorta and Iliac Artery.

“…Recently, Satoh et al (1998) Male albino rabbits weighing 2.0-3.0kg were anesthetized with an intravenous injection of pentobarbital sodium (50mg/kg) and killed by bleeding from the carotid arteries. Thoracic aorta and iliac arteries were quickly removed and dissected free of excess fat and connective tissue in oxygenated physiological saline solution (PSS) of the following composition (in millimoles): NaCl, 118; MgCl2, 1.2; CaCl2, 2.5; KH2PO4, 1.2; NaHCO3, 25 and glucose,…”