嘌呤生物合成途径抑制剂重氮丝氨酸、哈德酸和霉酚酸对发育中的绵羊黄体的影响。

Effects of the purine biosynthesis pathway inhibitors azaserine, hadacidin, and mycophenolic acid on the developing ovine corpus luteum.

作者信息

Miller-Patrick K, Vincent D L, Early R J, Weems Y S, Tanaka Y, Ashimine D T, Nusser K D, Lee C N, Ledgerwood K S, Weems C W

机构信息

Department of Animal Sciences, University of Hawaii at Manoa 96822.

出版信息

Chin J Physiol. 1993;36(4):245-52.

PMID:8020339

Abstract

De novo synthesis precursors of the purine second messengers adenosine, guanosine and inosine are adenosine, guanosine and inosine monophosphate (AMP, GMP, IMP), respectively. Inhibitors of the de novo purinergic synthesis pathways for AMP, GMP and IMP by hadacidin, mycophenolic acid and azaserine, respectively, or adenosine, guanosine or inosine alone or in combination were given every 4 or 6 hours in vivo. Treatments were given into the ovarian vascular pedicle sheath adjacent to the luteal-bearing ovary in three separate experiments to determine whether purines were involved in development of the corpus luteum. Hadacidin lowered AMP (p < or = 0.01) and azaserine tended to lower IMP and the GMP: AMP ratio (p < or = 01) while mycophenolic acid tended to lower the GMP:AMP ratio (p < or = 0.1) in luteal tissue. Azaserine (150 mg) increased progesterone (p < or = 0.01) on some days but guanosine or inosine had no effect on profiles of progesterone in jugular blood of the developing corpus luteum (p > or = 0.1). Azaserine (500 micrograms) tended to lower progesterone in jugular blood (p < or = 0.1) while profiles of progesterone did not differ among guanosine or inosine or adenosine, guanosine and inosine plus hadacidin, mycophenolic acid and azaserine treatment groups compared to controls (p > or = 0.1). Weights of corpora lutea or composition of cell types in the corpus luteum or their viability were not affected by adenosine, guanosine, inosine, hadacidin, mycophenolic acid or azaserine (p > or = 0.1). Since profiles of jugular progesterone did not differ between treatments during development of the corpus luteum, these results suggest that progesterone production by the developing corpus luteum is a) less dependent on de novo synthesized purines or b) there may be a non-purinergic-dependent second messenger system controlling biosynthesis of steroids in the developing ovine corpus luteum.

摘要

嘌呤第二信使腺苷、鸟苷和肌苷的从头合成前体分别是一磷酸腺苷（AMP）、一磷酸鸟苷（GMP）和一磷酸肌苷（IMP）。分别用杀稻瘟菌素、霉酚酸和重氮丝氨酸抑制AMP、GMP和IMP的嘌呤能从头合成途径，或者单独或联合给予腺苷、鸟苷或肌苷，在体内每4或6小时给药一次。在三个独立实验中，将药物注入与有黄体的卵巢相邻的卵巢血管蒂鞘内，以确定嘌呤是否参与黄体的发育。杀稻瘟菌素降低了黄体组织中的AMP（p≤0.01），重氮丝氨酸倾向于降低IMP和GMP:AMP比值（p≤0.1），而霉酚酸倾向于降低GMP:AMP比值（p≤0.1）。重氮丝氨酸（150毫克）在某些日子增加了孕酮水平（p≤0.01），但鸟苷或肌苷对发育中的黄体颈静脉血中孕酮水平无影响（p≥0.1）。重氮丝氨酸（500微克）倾向于降低颈静脉血中的孕酮水平（p≤0.1），而与对照组相比，鸟苷、肌苷、腺苷、鸟苷和肌苷联合杀稻瘟菌素、霉酚酸和重氮丝氨酸处理组的孕酮水平无差异（p≥0.1）。腺苷、鸟苷、肌苷、杀稻瘟菌素、霉酚酸或重氮丝氨酸对黄体重量、黄体细胞类型组成或其活力无影响（p≥0.1）。由于在黄体发育过程中各处理组的颈静脉孕酮水平无差异，这些结果表明，发育中的黄体产生孕酮：a）较少依赖从头合成的嘌呤；或b）可能存在一个非嘌呤能依赖的第二信使系统控制发育中的绵羊黄体中类固醇的生物合成。