Calcium mobilization by muscarinic receptors and ATP receptors during retinogenesis

乙酰胆碱和三磷酸腺苷（ATP）通过毒蕈碱受体和P_<2U>嘌呤受体，通过释放细胞内Ca^<2+>，提高细胞内Ca^<2+>浓度。我们用fura-2荧光测量研究了毒蕈碱和嘌呤能Ca^<2+>反应的信号转导机制以及嘌呤能Ca^<2+>反应的发育变化。百日咳毒素抑制atp诱导的Ca^<2+>升高，而对毒蕈碱Ca^<2+>升高无抑制作用。磷脂酶C抑制剂U-73122抑制Ca^<2+>上升到ATP，而类似物U-73343没有抑制作用。而U-73122和U-73343抑制了毒蕈碱Ca^<2+>的升高。Li^+抑制磷脂酰肌醇代谢，增强毒蕈碱和嘌呤能Ca^<2+>升高。Thapsigargin是肌醇三磷酸（IP_3）敏感Ca^<2+>储存的Ca^<2+>- atp酶抑制剂，可消除毒蕈碱和嘌呤能Ca^<2+>升高。毒蕈碱性和嘌呤能性Ca^<2+>动员之间发生串扰，但不闭塞。我们的研究表明，毒蕈碱和嘌呤能Ca^<2+>动员都利用了ip_3敏感的Ca^<2+>储存，但毒蕈碱和嘌呤能Ca^<2+>反应之间涉及不同的信号转导途径。atp诱导的Ca^<2+>升高在E3时最为显著，在E8时急剧下降，直至突触形成前的E11-13时进一步下降。在鸡视网膜神经发生的早期，ATP可能是细胞间的信使。

Acetylcholine and adenosine triphosphate (ATP) raise intracellular Ca^<2+> concentration via muscarinic receptors and P_<2U> purinoceptors by releasing Ca^<2+> from intracellular Ca^<2+> stores in the neural retina of early embryonic chick. We studied the signal transduction mechanisms for the muscarinic and purinergic Ca^<2+> responses and developmental changes in the purinergic Ca^<2+> responses with fura-2 fluorescence measurements.Pertussis toxin suppressed the ATP-induced Ca^<2+> rise, whereas no inhibition was observed on the muscarinic Ca^<2+> rise. U-73122, an inhibitor of phospholipase C,suppressed the Ca^<2+> rise to ATP,but its analog U-73343 did not suppress it. In contrast, both U-73122 and U-73343 suppressed the muscarinic Ca^<2+> rise. Li^+, which inhibits phosphatidylinositol metabolism, enhanced both the muscarinic and purinergic Ca^<2+> rises. Thapsigargin, an inhibitor of Ca^<2+>-ATPase of inositol trisphosphate (IP_3) -sensitive Ca^<2+> stores, abolished both the muscarinic and purinergic Ca^<2+> rises. Cross-talk occurred between the muscarinic and purinergic Ca^<2+> mobilizations but they were not occlusive. Our study suggests that both the muscarinic and purinergic Ca^<2+> mobilizations utilize IP_3-sensitive Ca^<2+> stores, but different signal transduction pathways are involved in between the muscarinic and purinergic Ca^<2+> responses.The ATP-induced Ca^<2+> rise was the most prominent at E3, drastically declined towards E8 and further decreased until E11-13 before synapse formation. ATP might act as an intercellular messenger during the early period of neurogenesis in the chick retina.