Barajas-López C, Peres A L, Espinosa-Luna R
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Am J Physiol. 1996 Jul;271(1 Pt 1):C264-75. doi: 10.1152/ajpcell.1996.271.1.C264.
Whole cell recordings were used to investigate the effects of adenosine and several of its analogues on voltage-activated calcium currents (VACC) of myenteric and submucosal neurons. Electrophysiological and pharmacological properties of the soma VACC recorded in myenteric neurons indicate that they are carried through N-type calcium channels, similar to those of the submucosal neurons and to those of the calcium conductance that mediates acetylcholine release at the submucosal ganglia. Adenosinergic compounds inhibited, in a concentration-response and in a voltage-dependent manner, VACC in neurons from both enteric plexuses. The pharmacological profile of the receptors that mediate this effect was similar to that of the receptors involved in presynaptic inhibition in enteric neurons and likely of the A1 subtype. The effects of 2-chloroadenosine (CADO) on VACC were prevented by pretreatment with pertussis toxin (PTX), became irreversible with guanosine 5'-O-(3-thiotriphosphate) (inside the pipette), and were abolished with N-ethylmaleimide (NEM; known to uncouple receptors from G protein complexes). Intracellular recordings were used to further evaluate presynaptic effects of adenosine at the submucosal plexus. Adenosinergic compounds reduced the amplitude of fast excitatory postsynaptic potentials (EPSPs) by acting at nerve terminals. This effect was insensitive to PTX and staurosporine (a protein kinase inhibitor) but was abolished by NEM. CADO effects on EPSPs were not reversed by increasing the extracellular calcium concentration. In conclusion, activation of A1 adenosine receptors inhibits VACC via PTX-sensitive G proteins in myenteric and submucosal neurons. Reduction of cholinergic transmission also involves A1 adenosine receptors and appears to involve the activation of PTX-insensitive G proteins.
采用全细胞记录法研究腺苷及其几种类似物对肠肌间神经丛和黏膜下神经节神经元电压门控性钙电流（VACC）的影响。在肠肌间神经丛神经元中记录到的胞体VACC的电生理和药理学特性表明，它们是通过N型钙通道传导的，这与黏膜下神经节神经元以及介导黏膜下神经节乙酰胆碱释放的钙电导类似。腺苷能化合物以浓度依赖性和电压依赖性方式抑制两个肠神经丛神经元的VACC。介导此效应的受体的药理学特征与肠神经元突触前抑制所涉及的受体相似，可能属于A1亚型。用百日咳毒素（PTX）预处理可阻断2-氯腺苷（CADO）对VACC的作用，用鸟苷5'-O-（3-硫代三磷酸）（吸管内）处理后该作用变为不可逆，而用N-乙基马来酰亚胺（NEM；已知可使受体与G蛋白复合物解偶联）处理则可消除此作用。采用细胞内记录法进一步评估腺苷在黏膜下神经丛的突触前效应。腺苷能化合物通过作用于神经末梢降低快速兴奋性突触后电位（EPSP）的幅度。此效应对PTX和星形孢菌素（一种蛋白激酶抑制剂）不敏感，但可被NEM消除。增加细胞外钙浓度不能逆转CADO对EPSP的作用。总之，A1腺苷受体的激活通过PTX敏感的G蛋白抑制肠肌间神经丛和黏膜下神经节神经元的VACC。胆碱能传递的减少也涉及A1腺苷受体，且似乎涉及PTX不敏感的G蛋白的激活。
