Okada Yukio, Imendra Kotapola G, Miyazaki Toshihiro, Hotokezaka Hitoshi, Fujiyama Rie, Zeredo Jorge L, Toda Kazuo
Integrative Sensory Physiology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, Nagasaki 852-8588, Japan.
Cell Mol Neurobiol. 2007 Sep;27(6):771-81. doi: 10.1007/s10571-007-9171-z. Epub 2007 Jul 17.
The effect of calcium-sensing receptor (CaR) agonists on frog gustatory responses was studied using glossopharyngeal nerve recording and whole-cell patch-clamp recording of isolated taste disc cells. Calcimimetic NPS R-467 dissolved in normal saline solution elicited a large transient response in the nerve. The less active enantiomer of the compound, NPS S-467 induced only a small neural response. The EC(50) for NPS R-467 was about 20 microM. Cross-adaptation experiments were performed to examine the effect of 30 microM NPS R-467 and 100 microM quinine on the gustatory neural response. The magnitude of the R-467-induced response after adaptation to quinine was approximately equal to that after adaptation to normal saline solution, indicating that the receptor site for NPS R-467 is different from the site for quinine. NPS R-467 (100 microM) also induced an inward current accompanied with conductance increase and large depolarization in two (13%) of 15 rod cells, and a sustained decrease in outward current and small depolarization in six (40%) other rod cells. NPS S-467 (100 microM) induced a sustained decrease in outward current and depolarization in five (50%) of 10 rod cells. Another calcimimetic cinacalcet (100 microM) induced an inward current accompanied with conductance increase in three (27%) of 11 rod cells. The results suggest that NPS R-467 induces neural responses through cell responses unrelated to a resting K(+) conductance decrease.
利用舌咽神经记录和分离的味觉盘细胞的全细胞膜片钳记录，研究了钙敏感受体（CaR）激动剂对青蛙味觉反应的影响。溶解于生理盐水的拟钙剂NPS R - 467在神经中引发了一个大的瞬时反应。该化合物活性较低的对映体NPS S - 467仅诱导出小的神经反应。NPS R - 467的半数有效浓度（EC50）约为20微摩尔。进行交叉适应实验以检测30微摩尔NPS R - 467和100微摩尔奎宁对味觉神经反应的影响。适应奎宁后R - 467诱导反应的幅度与适应生理盐水溶液后的幅度大致相等，表明NPS R - 467的受体位点与奎宁的位点不同。NPS R - 467（100微摩尔）还在15个杆状细胞中的2个（13%）中诱导出内向电流，伴有电导增加和大的去极化，在另外6个（40%）杆状细胞中诱导出外向电流持续减少和小的去极化。NPS S - 467（100微摩尔）在10个杆状细胞中的5个（50%）中诱导出外向电流持续减少和去极化。另一种拟钙剂西那卡塞（100微摩尔）在11个杆状细胞中的3个（27%）中诱导出内向电流，伴有电导增加。结果表明，NPS R - 467通过与静息钾电导降低无关的细胞反应诱导神经反应。
