Bardou M, Dousset B, Deneux-Tharaux C, Smadja C, Naline E, Chaput J C, Naveau S, Manara L, Croci T, Advenier C
Département de Pharmacologie, Faculté de Médecine Paris-Ouest, France.
Eur J Pharmacol. 1998 Jul 24;353(2-3):281-7. doi: 10.1016/s0014-2999(98)00419-1.
The new beta3-adrenoceptor is present in the gastrointestinal tract of various species. This study aimed to show that this receptor modulates human colonic motility in vitro. We used circular muscle strips from the human colon suspended in single organ baths containing Krebs solution and subjected to an initial 1.5-2 g tension. We measured the effects of different beta3-adrenoceptor agonists, including SR 59104A (N-[(6-hydroxy-1,2,3,4-tetrahydronaphthalen-(2R)-2-yl)methyl]-(2 R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), SR 59119A (N-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-(2R)-2-yl)methyl]-(2R) -2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), BRL 37344 (R,R + S,S) [4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl] phenoxy] acetic acid), and of isoprenaline and salbutamol in the absence or in the presence of propranolol alone or in combination with the beta3-adrenoceptor antagonist SR 59230A (3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydro-naphthalen-1- ylamino]-(2S)-2-propanol oxalate) on amplitude of spontaneous contractions. To evaluate a possible beta2-adrenoceptor-mediated effect, we studied the action of these compounds on human isolated bronchi. On the human isolated colon, SR 59119A, SR 59104A and isoprenaline reduced the initial amplitude of spontaneous contractions by 60%. The curves obtained in the presence of antagonists suggested an action mediated by beta3-adrenoceptor stimulation, since propranolol did not antagonize the action of SR 59119A and SR 59104A, whereas the combination of propranolol and SR 59230A significantly displaced the concentration-response curve of these agonists to the right. This study provides pharmacological evidence of modulation of human colonic motility, and especially of the amplitude of spontaneous contractions, by the atypical beta-adrenoceptor, the beta3-adrenoceptor.
新型β3 - 肾上腺素能受体存在于多种物种的胃肠道中。本研究旨在表明该受体在体外调节人类结肠运动。我们使用从人类结肠获取的环形肌条，将其悬浮于含有 Krebs 溶液的单个器官浴槽中，并施加初始 1.5 - 2 克的张力。我们测量了不同β3 - 肾上腺素能受体激动剂的作用，包括 SR 59104A（N - [(6 - 羟基 - 1,2,3,4 - 四氢萘 - (2R) - 2 - 基)甲基] - (2R) - 2 - 羟基 - 2 - (3 - 氯苯基)乙胺盐酸盐）、SR 59119A（N - [(7 - 甲氧基 - 1,2,3,4 - 四氢萘 - (2R) - 2 - 基)甲基] - (2R) - 2 - 羟基 - 2 - (3 - 氯苯基)乙胺盐酸盐）、BRL 37344（R,R + S,S）[4 - [2 - [[2 - (3 - 氯苯基) - 2 - 羟乙基] - 氨基]丙基]苯氧基]乙酸），以及在单独使用普萘洛尔或与β3 - 肾上腺素能受体拮抗剂 SR 59230A（3 - (2 - 乙基苯氧基) - 1 - [(1S) - 1,2,3,4 - 四氢萘 - 1 - 基氨基] - (2S) - 2 - 丙醇草酸盐）联合使用或不使用普萘洛尔的情况下，异丙肾上腺素和沙丁胺醇对自发收缩幅度的影响。为评估可能的β2 - 肾上腺素能受体介导的效应，我们研究了这些化合物对人离体支气管的作用。在人离体结肠上，SR 59119A、SR 59104A 和异丙肾上腺素使自发收缩的初始幅度降低了 60%。在拮抗剂存在下获得的曲线表明这是由β3 - 肾上腺素能受体刺激介导的作用，因为普萘洛尔不拮抗 SR 59119A 和 SR 59104A 的作用，而普萘洛尔与 SR 59230A 的组合显著使这些激动剂的浓度 - 反应曲线右移。本研究提供了非典型β - 肾上腺素能受体即β3 - 肾上腺素能受体调节人类结肠运动，尤其是自发收缩幅度的药理学证据。
