Differential effects of resact analogues on sperm respiration rates and cyclic nucleotide concentrations.
Differential effects of resact analogues on sperm respiration rates and cyclic nucleotide concentrations.
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React 类似物对精子呼吸速率和环核苷酸浓度的不同影响。
DOI：
10.1021/bi00359a046
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发表时间：
1986
期刊：
影响因子：
2.9
通讯作者：
Garbers,DL
中科院分区：
文献类型：
--
作者：
Shimomura,H;Garbers,DL
修订稿于 1986 年 2 月 10 日收到 摘要：合成了 resact 的类似物 (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-LeuNH2)，以确定是否可以独立于环核苷酸浓度的升高而获得对精子呼吸的刺激。 CO2末端亮氨酸NH2的修饰不会改变生物活性；然而，用 Ser 或 Tyr 取代两个半胱氨酰残基或半胱氨酰残基甲基化会导致不同的相对效力，具体取决于是否测量呼吸速率或环核苷酸浓度。 例如，[Ser1, Tyr8] resact 在刺激呼吸速率方面的效力约为 resact 的 40%，但在引起环 GMP 升高方面的效力仅为 resact 的 1%。 NH2末端片段(Cys-Val-Thr-Gly-Ala-Pro-Gly)在浓度高达10μ时既不刺激呼吸也不升高环核苷酸水平，而CO2末端片段(Cys-Val-Gly-Gly-Gly-Arg-LeuNH2)具有resact的约20%的呼吸活性和0.1%的环GMP提升活性。然而，当同时添加CO 2 -和NH 2 -末端片段时，环核苷酸浓度以与用resact观察到的相同相对浓度升高。随后合成了类似物（‘25I-[Tyr1, Ser8] resact）并用于受体结合研究。 NH 2 末端和CO 2 末端片段都竞争结合，尽管它们的有效性分别是resact的0.0004和0.025倍。然而，在竞争性结合测定中，在 1 µ resact-(l-7) 存在的情况下，resact-(8-14) 几乎与 resact 一样有效。因此，各个CO 2 和NH 2 末端片段似乎各自与受体结合，但其中一个片段的存在极大地增强了另一个肽片段的结合。环核苷酸升高似乎可以与呼吸刺激分开，这表明环 AMP 或环 GMP 浓度的增加不会介导肽对呼吸的影响。许多不同动物（包括人类）的卵子和/或雌性生殖道的分泌物似乎可以刺激精子的代谢和运动（Garbers 和 Kopf，1980）。在哺乳动物中，在兔子、豚鼠、小鼠、蝙蝠、海豚、仓鼠、狗、牛、羊和人类中观察到精子活力过度活跃（Yanagimachi, 1970, 1972; Phillips, 1972; Barros et al., 1973; Yanagimachi & Usui, 1974; Mahi & Yanagimachi, 1976；Aonuma 等，1980；Lambert 等，1982；Mor-timer 等，1983；因此，如果代谢或运动激活对于受精很重要，那么干预可能具有农业或医学应用。在我们的实验室中，从海胆卵中分离出两类肽，可刺激精子的呼吸速率和活力（Hansbrough & Garbers，1981；Garbers 等，1982；Suzuki 等，1984）。从 Arbacia punctulata 中分离的肽被命名为 resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-LeuNH2)，从 Strongylocen-trotus purpuratus 中获得的肽被命名为 speract （Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly）（Hansbrough & Garbers，1981a；Garbers 等人，1982；Suzuki 等人，1984）。 Speract 也已从 Hemicentrotus pulcherrimus 卵中分离出来（Suzuki 等，1981）。这些肽（speract 和 resact）以物种特异性方式增加精子环 AMP 和环 GMP 浓度（Suzuki 等，1984；Suzuki &
Revised Manuscript Received February 10, 1986 abstract: Analogues of resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-LeuNH2) were synthesized to determine whether or not a stimulation of sperm respiration could be obtained independent of elevations of cyclic nucleotide concentrations. Modification of the C02-terminal leucine NH2 did not alter biological activity; however, substitution of the two cysteinyl residues by Ser or Tyr or methylation of the cysteinyl residues resulted in divergent relative potencies dependent on whether respiration rates or cyclic nucleotide concentrations were measured.[Ser1, Tyr8] resact, as an example, was approximately 40% as potent as resact at stimulating respiration rates but was 1% as effective as resact at causing cyclic GMP elevations. An NH2-terminal fragment (Cys-Val-Thr-Gly-Ala-Pro-Gly) neither stimulated respiration nor elevated cyclic nucleotide levels at concentrations up to 10 µ whereas a C02-terminal fragment (Cys-Val-Gly-Gly-Gly-Arg-LeuNH2) had approximately 20% of the respirationactivity and 0.1% of the cyclic GMP elevating activity of resact. When the C02-and NH2-terminal fragments were added simultaneously, however, cyclic nucleotide concentrations were elevated at the same relative concentrations as observed with resact. An analogue (‘25I-[Tyr1, Ser8] resact) was subsequently synthesized and used for receptor binding studies. Both the NH2-terminal and C02-terminal fragments competed for binding, although they were 0.0004 and 0.025 times as effective as resact, respectively. However, in the presence of 1 µ resact-(l-7), resact-(8-14) was almost as potent as resact in the competitive binding assay. The individual C02-and NH2-terminal fragments appear to each bind to receptor, therefore, but the presence of one greatly potentiates the binding of the other peptide fragment. It also appears that cyclic nucleotideelevations can be separated from the stimulation of respiration, suggestive that increased concentrations of cyclic AMP or cyclic GMP do not mediate the effects of the peptides on respiration.Eggs and/or secretions of the female reproductive tract from many different animals, including the human, appearto stimulate spermatozoan metabolism and motility (Garbers & Kopf, 1980). In mammals, a hyperactivated form of sperm motility has been observed in rabbits, guineapigs, mice, bats, dolphins, hamsters, dogs, cattle, sheep, and humans (Yanagimachi, 1970, 1972; Phillips, 1972; Barros et al., 1973; Yanagimachi & Usui, 1974; Mahi & Yanagimachi, 1976; Cooper et al., 1979; Aonuma et al., 1980; Johnson et al., 1980; Lambert, 1981; Cummins, 1982; Fleming et al., 1982; Mor-timer et al., 1983); therefore, if metabolic or motility activation is important for fertilization, interventionmay have agricul-tural or medical applications. In our laboratory, two classes of peptides have been isolated from sea urchin eggs that stimulate sperm respiration rates and motility (Hansbrough & Garbers, 1981; Garbers et al., 1982; Suzuki et al., 1984). A peptide isolated from Arbacia punctulata has been named resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-LeuNH2), and a peptide obtained from Strongylocen-trotus purpuratus has been called speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly)(Hansbrough & Garbers, 1981a; Garbers et al., 1982; Suzuki et al., 1984). Speract also has been isolated from Hemicentrotus pulcherrimus eggs (Suzuki et al., 1981). These peptides (speract and resact) increase sperm cyclic AMP and cyclic GMP concentrations in a species-specific manner(Suzuki et al., 1984; Suzuki &
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speract 和莫能菌素对海胆精子的钠依赖性激活。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hansbrough,JR;Garbers,DL
通讯作者：
Garbers,DL
9 – 后生动物中精子的化学取向
DOI：
--
发表时间：
1985
期刊：
影响因子：
--
作者：
Richard L. Miller
通讯作者：
Richard L. Miller
影响因子：
1.7
作者：
S. Aonuma;M. Okabe;M. Kawaguchi;Y. Kishi
通讯作者：
Y. Kishi
受精生物学
DOI：
--
发表时间：
1985
期刊：
影响因子：
--
作者：
C. B. Metz;A. Monroy
通讯作者：
A. Monroy
影响因子：
64.8
作者：
HUNTER, WM;GREENWOOD, FC
通讯作者：
GREENWOOD, FC