Fornai M, Antonioli L, Colucci R, Ghisu N, Buccianti P, Marioni A, Chiarugi M, Tuccori M, Blandizzi C, Del Tacca M
Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Pisa, Italy.
Neurogastroenterol Motil. 2009 Apr;21(4):451-66. doi: 10.1111/j.1365-2982.2008.01213.x. Epub 2008 Oct 25.
Experimental evidence in animal models suggests that adenosine is involved in the regulation of digestive functions. This study examines the influence of adenosine on the contractile activity of human colon. Reverse transcription-polymerase chain reaction revealed A(1) and A(2a) receptor expression in colonic neuromuscular layers. Circular muscle preparations were connected to isotonic transducers to determine the effects of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A(1) receptor antagonist), ZM 241385 (A(2a) receptor antagonist), CCPA (A(1) receptor agonist) and 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamide-adenosine (CGS 21680; A(2a) receptor agonist) on motor responses evoked by electrical stimulation or carbachol. Electrically evoked contractions were enhanced by DPCPX and ZM 241385, and reduced by CCPA and CGS 21680. Similar effects were observed when colonic preparations were incubated with guanethidine (noradrenergic blocker), L-732,138, GR-159897 and SB-218795 (NK receptor antagonists). However, in the presence of guanethidine, NK receptor antagonists and N(omega)-propyl-L-arginine (NPA; neuronal nitric oxide synthase inhibitor), the effects of DPCPX and CCPA were still evident, while those of ZM 241385 and CGS 21680 no longer occurred. Carbachol-induced contractions were unaffected by A(2a) receptor ligands, but they were enhanced or reduced by DPCPX and CCPA, respectively. When colonic preparations were incubated with guanethidine, NK antagonists and atropine, electrically induced relaxations were partly reduced by ZM 241385 or NPA, but unaffected by DPCPX. Dipyridamole or application of exogenous adenosine reduced electrically and carbachol-evoked contractions, whereas adenosine deaminase enhanced such motor responses. In conclusion, adenosine exerts an inhibitory control on human colonic motility. A(1) receptors mediate direct modulating actions on smooth muscle, whereas A(2a) receptors operate through inhibitory nitrergic nerve pathways.
动物模型中的实验证据表明，腺苷参与消化功能的调节。本研究考察了腺苷对人结肠收缩活性的影响。逆转录-聚合酶链反应显示结肠神经肌肉层中有A(1)和A(2a)受体表达。环形肌制备物连接到等张换能器上，以确定8-环戊基-1,3-二丙基黄嘌呤（DPCPX；A(1)受体拮抗剂）、ZM 241385（A(2a)受体拮抗剂）、CCPA（A(1)受体激动剂）和2-[(对-2-羧乙基)-苯乙氨基]-5'-N-乙基-羧酰胺腺苷（CGS 21680；A(2a)受体激动剂）对电刺激或卡巴胆碱诱发的运动反应的影响。DPCPX和ZM 241385增强电诱发的收缩，CCPA和CGS 21680则使其减弱。当结肠制备物与胍乙啶（去甲肾上腺素能阻滞剂）、L-732,138、GR-159897和SB-218795（NK受体拮抗剂）一起孵育时，观察到类似的效果。然而，在存在胍乙啶、NK受体拮抗剂和N(ω)-丙基-L-精氨酸（NPA；神经元型一氧化氮合酶抑制剂）的情况下，DPCPX和CCPA的作用仍然明显，而ZM 241385和CGS 21680的作用不再出现。卡巴胆碱诱发的收缩不受A(2a)受体配体的影响，但分别被DPCPX和CCPA增强或减弱。当结肠制备物与胍乙啶、NK拮抗剂和阿托品一起孵育时，电诱发的舒张部分被ZM 241385或NPA减弱，但不受DPCPX影响。双嘧达莫或应用外源性腺苷可减弱电刺激和卡巴胆碱诱发的收缩，而腺苷脱氨酶则增强这种运动反应。总之，腺苷对人结肠运动起抑制性调控作用。A(1)受体介导对平滑肌的直接调节作用，而A(2a)受体则通过抑制性一氧化氮能神经通路发挥作用。
