Analysis of the neuroendocrine system in PAC1 knock out mice

采用PAC1受体缺陷雄性小鼠（PAC1-/-）研究垂体腺苷酸环化酶激活多肽（PACAP） I型受体（PAC1受体）在调节下丘脑视上神经元中的作用。研究了PACAP对新解离的视上神经元中[Ca2+]i的影响，以及在完整的视上核中对垂体后叶加压素和催产素的体树突释放的影响。在野生型小鼠（PAC1+/+）的视上神经元中，100 nm PACAP诱导[Ca2+]i的增加和加压素和催产素的释放，而在杂合子（PAC1+/-）和零突变小鼠（PAC1-/-）中，PACAP的作用要小得多。PACAP应用于PAC1 +/+、PAC1-/-小鼠和大鼠离体神经垂体神经末梢时，对这两个参数无影响。综上所述，PAC1受体单独负责pacap诱导的[Ca2+]i信号传导和视上神经元体突区加压素和催产素的分泌。

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor (PAC1 receptor) in regulating hypothalamic supraoptic neurones was investigated using PAC1 receptor-deficient male mice (PAC1-/-). The effects of PACAP on [Ca2+]i were investigated in freshly dissociated supraoptic neurones and on the somatodendritic release of vasopressin and oxytocin, examined on intact supraoptic nuclei. In supraoptic neurones from wild-type mice (PAC1+/+), 100 nm PACAP induced an increase in [Ca2+]i and release of vasopressin and oxytocin, whereas in heterozygous (PAC1+/-) and null-mutant mice (PAC1-/-), PACAP was much less effective. PACAP had no effect on these two parameters when applied to isolated neurohypophysial nerve terminals of PAC l+/+ and PAC1-/- mice, and rats. In conclusion, the PAC1 receptor is solely responsible for the PACAP-induced [Ca2+]i signalling and secretion of vasopressin and oxytocin in the somatodendritic region of supraoptic neurones.