Tomiyama Y, Hayakawa K, Shinagawa K, Akahane M, Ajisawa Y, Park Y C, Kurita T
Division of Discovery Research, Kissei Pharmaceutical, Hotaka, Nagano, Japan.
Eur J Pharmacol. 1998 Jul 10;352(2-3):269-78. doi: 10.1016/s0014-2999(98)00360-4.
We investigated the beta-adrenoceptor subtypes mediating ureteral relaxation in rats, rabbits and dogs. The relaxing effects of beta-adrenoceptor agonists were evaluated on KCl-induced ureteral contractions. The rank order of potency of the catecholamines tested was isoprenaline > noradrenaline > adrenaline in rat ureter; isoprenaline > adrenaline > noradrenaline in rabbit ureter; only isoprenaline was effective in canine tissues. The beta1-adrenoceptor agonist, dobutamine, produced relaxation of rat ureter. The beta2-adrenoceptor agonist, procaterol, produced more significant relaxation of rabbit ureter than did dobutamine. CL-316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-b enzodioxole-2,2-dicarboxylate] and CGP-12177A [(+/-)[4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-+ ++benzimidazol-2-one hydrochloride], beta3-adrenoceptor agonists, were more effective in relaxing canine ureter than were dobutamine and procaterol. Isoprenaline-induced relaxation was antagonized by a beta1-adrenoceptor antagonist, CGP-20712A [2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidazol e-2-yl)phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate], in rats and by a beta2-adrenoceptor antagonist, ICI-118,551 [(+/-)-1-[(2,3-dihydro-7-methyl- 1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride], in rabbits. The non-selective beta-adrenoceptor antagonist, bupranolol, antagonized isoprenaline-induced relaxation in all species tested. In conclusion, beta-adrenoceptor agonists may relax ureter by stimulating mainly beta1-adrenoceptors in rats, beta2-adrenoceptors in rabbits and mainly beta3-adrenoceptors in dogs.
我们研究了介导大鼠、兔和犬输尿管舒张的β-肾上腺素能受体亚型。评估了β-肾上腺素能受体激动剂对氯化钾诱导的输尿管收缩的舒张作用。在所测试的儿茶酚胺中,效力顺序在大鼠输尿管中为异丙肾上腺素>去甲肾上腺素>肾上腺素;在兔输尿管中为异丙肾上腺素>肾上腺素>去甲肾上腺素;在犬组织中只有异丙肾上腺素有效。β1-肾上腺素能受体激动剂多巴酚丁胺可使大鼠输尿管舒张。β2-肾上腺素能受体激动剂丙卡特罗比多巴酚丁胺更显著地使兔输尿管舒张。β3-肾上腺素能受体激动剂CL-316243[(R,R)-5-[2-[[2-(3-氯苯基)-2-羟乙基氨基]丙基]-1,3-苯并二恶唑-2,2-二羧酸酯]和CGP-12177A[(±)[4-[3[(1,1-二甲基乙基)氨基]-2-羟基丙氧基]-1,3-二氢-2H-苯并咪唑-2-酮盐酸盐]在舒张犬输尿管方面比多巴酚丁胺和丙卡特罗更有效。异丙肾上腺素诱导的舒张在大鼠中被β1-肾上腺素能受体拮抗剂CGP-20712A[2-羟基-5(2-((2-羟基-3-(4-((1-甲基-4-三氟甲基)-1H-咪唑-2-基)苯氧基)丙基)氨基)乙氧基)-苯甲酰胺甲磺酸盐]拮抗,在兔中被β2-肾上腺素能受体拮抗剂ICI-118,551[(±)-1-[(2,3-二氢-7-甲基-1H-茚-4-基)氧基]-3-[(1-甲基乙基)氨基]-2-丁醇盐酸盐]拮抗。非选择性β-肾上腺素能受体拮抗剂布普洛尔在所有测试物种中均拮抗异丙肾上腺素诱导的舒张。总之,β-肾上腺素能受体激动剂可能主要通过刺激大鼠的β1-肾上腺素能受体、兔的β2-肾上腺素能受体和犬的β3-肾上腺素能受体来舒张输尿管。