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• W2073908817 abstract "1 The affinities of a number of α1 -adrenoceptor antagonists were determined by displacement of [3H]-prazosin binding from cloned human α1A-adrenoceptors (previously designated cloned α1c subtype), α1B α1D and rat α1D-adrenoceptors, stably expressed in rat-1 fibroblasts. Functional affinity estimates for these compounds were also determined from noradrenaline-mediated contractions of rat aorta. 2 BMY 7378 displayed high affinity for cloned human α1D-adrenoceptors (pKi = 8.2 ±0.10) and was selective over α1A (pAi = 6.2 ±0.10) and α1B subtypes (6.7 ± 0.11). WB 4101, benoxathian and phentolamine displayed high affinity for α1A and α1D adrenoceptors compared to the α1B subtype. Spiperone displayed high affinity and selectivity for α1B adrenoceptors (pKi 8.8 ±0.16). 5-Methyl-urapidil was selective for cloned α1A adrenoceptors. 3 Comparative binding affinities (pKi for compounds at cloned human and rat1D adrenoceptors were almost identical (r = 0.99, slope =1.08). 4 Prazosin, doxazosin and 5-methyl-urapidil were potent, competitive antagonists of noradrenaline-mediated contractions of rat aorta (pA2 values of 9.8, 8.8 and 7.8 respectively). The selective α1D antagonist BMY 7378 was also a potent antagonist on rat aorta (pKB = 8.3±0.1) but the interaction of this compound was not consistent with competitive antagonism at a single population of receptors. 5 Functional affinities for compounds determined against noradrenaline-mediated contractions of rat aorta correlated well with binding affinities at cloned α1D-adrenoceptors (r = 0.96), but not with α1A (r = 0.61) or α1B (r = 0.46) subtypes. 6 Noradrenaline-mediated contractions of rat aorta were sensitive to the alkylating effects of chlorethylclonidine (CEC). CEC (10 μm) caused a small rightward shift in the noradrenaline concentration-response curve. CEC at 100 μm caused a further shift and suppression of the maximum response to noradrenaline. 7 The results of this study suggest that noradrenaline predominantly, but not exclusively, mediates contraction of rat aorta through the activation of an α1D-adrenoceptor." @default.
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• W2073908817 date "1995-07-01" @default.
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• W2073908817 title "Characterization of an α1D-adrenoceptor mediating the contractile response of rat aorta to noradrenaline" @default.
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• W2073908817 doi "https://doi.org/10.1111/j.1476-5381.1995.tb15907.x" @default.
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