Respiratory activity is under circadian modulation and the physiological mechanisms may involve the pineal secretory product, melatonin, and the carotid chemoreceptor. We hypothesized that melatonin modulates the carotid chemoreceptor response to hypercapnic acidosis. To determine whether the effect of melatonin on the chemoreceptor response to hypercapnic acidosis is mediated by melatonin receptors in the chemosensitive cells, cytosolic calcium ([Ca2+]i) was measured by spectrofluorometry in fura-2-loaded glomus cells dissociated from rat carotid bodies. Melatonin (0.01-10 nm) per se did not change the [Ca2+]i levels of the glomus cells but it concentration-dependently attenuated the peak [Ca2+]i response to hypercapnic acidosis in the glomus cells. In addition, the [Ca2+]i response was attenuated by 2-iodomelatonin, an agonist of melatonin receptors. The melatonin-induced attenuation of the [Ca2+]i response to hypercapnic acidosis was abolished by pretreatment with an non-selective mt1/MT2 antagonist, luzindole, and by MT2 antagonists, 4-phenyl-2-propionamidotetraline or DH97. In situ hybridization study with antisense mt1 and MT2 receptor mRNA oligonucleotide probes showed an expression of mt1 and MT2 receptors in the rat carotid body. Also, melatonin attenuated the carotid afferent response to hypercapnic acidosis in single- or pauci-fibers recorded from the sinus nerve in isolated carotid bodies superfused with bicarbonate-buffer saline. Results suggest that an activation of the melatonin receptors expressed in the glomus cells of the rat carotid body reduces the chemoreceptor response to hypercapnic acidosis. This modulation may play a physiological role in the influence of the circadian rhythms on the chemoreflex.

中文翻译：

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褪黑素减弱大鼠对高碳酸血症性酸中毒的化学感受器反应。

呼吸活动处于昼夜节律调节下，其生理机制可能涉及松果体分泌产物，褪黑激素和颈动脉化学感受器。我们假设褪黑素调节对高碳酸血症性酸中毒的颈动脉化学感受器反应。为了确定褪黑素对高碳酸血症性中毒的化学感受器反应的影响是否是由化学敏感性细胞中的褪黑素受体介导的，通过分光光度法测定了从大鼠颈动脉体分离出的呋喃2负载的glomus细胞中的胞质钙（[Ca2 +] i）。褪黑素（0.01-10 nm）本身并没有改变血管球细胞的[Ca2 +] i水平，但是它浓度依赖性地减弱了血管球细胞对高碳酸血症性酸中毒的峰值[Ca2 +] i反应。此外，[io2]褪黑素减弱了[Ca2 +] i反应，褪黑激素受体激动剂。褪黑素诱导的[Ca2 +] i对高碳酸血症性酸中毒的减弱通过用非选择性mt1 / MT2拮抗剂Luzindole和MT2拮抗剂4-phenyl-2-propionamidotetraline或DH97预处理而被消除。用反义mt1和MT2受体mRNA寡核苷酸探针进行的原位杂交研究显示了大鼠颈动脉中mt1和MT2受体的表达。此外，褪黑素减弱了在单独的颈动脉体中充注有碳酸氢盐缓冲液的鼻窦神经中记录的单纤维或丘脑纤维对高碳酸血症性酸中毒的颈动脉传入反应。结果表明，在大鼠颈动脉体球状细胞中表达的褪黑激素受体的激活降低了对高碳酸血症性酸中毒的化学受体反应。