Wistar大鼠和RCS大鼠视网膜色素上皮细胞和视杆细胞外节表面Con－A受体

为探讨正常大鼠与吞噬功能缺陷大鼠视网膜色素上皮（ＲＰＥ）和视杆细胞外节（ＲＯＳ）膜表面的甘露糖受体的存在和分布,本实验用胶体金标记物对１２只Ｗｉｓｔａｒ大鼠和１２只ＲＣＳ大鼠的ＲＰＥ细胞及临近其顶部的ＲＯＳ表面的Ｃｏｎ－Ａ受体进行标记．结果表明。两种大鼠ＲＰＥ细胞及ＲＯＳ膜表面均有胶体金标记物．胶体金标记物在两种ＲＰＥ细胞微绒毛上分布密度较低,而在两种大鼠ＲＯＳ膜表面分布密度则高。说明两种大鼠ＲＰＥ细胞和ＲＯＳ膜表面均有Ｃｏｎ－Ａ受体分布。在两种大鼠ＲＯＳ被ＲＰＥ细胞吞入后,均无胶体金标记物。     

Ghrelin and GHRP-6 enhance electrical and secretory activity in GC somatotropes

It is well established that pituitary somatotropes fire spontaneous action potentials (SAP) which generate Ca(2+) signals of sufficient amplitude to trigger growth hormone (GH) release. It is also known that ghrelin and synthetic GH-releasing peptides (GHRPs) stimulate GH secretion, though the mechanisms involved remain unclear. In the current report, we show that the chronic (96h) treatment with ghrelin and GHRP-6 increases the firing frequency of SAP in the somatotrope GC cell line. This action is associated with a significant increase in whole-cell inward current density. In addition, long-term application of Na(+) or L-type Ca(2+) current antagonists decreases GHRP-6-induced release of GH, indicating that the ionic currents that give rise to SAP play important roles for hormone secretion in the GC cells. Together, our results suggest that ghrelin and GHPR-6 may increase whole-cell inward current density thereby enhancing SAP firing frequency and facilitating GH secretion from GC somatotropes.     

Utilization of some non coded amino acids as isosters of peptide building blocks

Summary In our study on non coded amino acids and their utilization in peptide chemistry we synthesized methylene-thio (CH₂—S) and methyleneoxy (CH₂—O) group containing amino acids and pseudodipeptides which could be used as building blocks for the construction of peptide hormone analogues. The (CH₂—S) isoster of peptide bond exhibits increased flexibility, lipophility and resistance to proteolytic enzymes. This group exhibits similar properties as the isosteric disulfide bond in the side chain of cystine residue. The (CH₂—O) isoster is moreover similar in its geometry to extended conformation of peptide bond. As a consequence, the changed profile of biological activities could be expected for peptide hormone analogues containing such isosteric moiety. The (CH₂—S) isosters of the peptide bond were prepared by alkylation of thiolates of 2-mercaptocarboxylic acids, the disulfide bond by alkylation of cysteine or homocysteine. The (CH₂—O) isosters were prepared by (AcO)₄Rh₂ catalyzed addition of carbenes of alkyl diazocarboxylates to N-protected aminoalcohols. Pseudodipeptides H—Leu—(CH₂—S)—Gly—NH₂ and H—Leu—(CH₂—O)—Gly—NH₂ were introduced into the C-terminal part of the oxytocin molecule using solution methods of peptide chemistry. Both inserted isosteric bonds were resistant against proteolytic degradation, the first one was found to decrease an enzymic cleavage of the distant Tyr²-Ile³ bond in the corresponding analogue, too. The (CH₂—S) isosters of the disulfide bond containing an orthogonal protection of their-amino (Fmoc) and-(OAll, OH) or-(OBu⁺, OH) carboxylic groups were applied in the solid phase synthesis of the aminoterminal 1-deamino-15-pentadecapeptide of endothelin-I which represents a strong vasoactive agent. The solid phase synthesis was carried out by the step-wise protocol on the Rink or Merrifield type resin using orthogonally protected carba cystine building blocks.     

生长激素释放肽的合成及促生长活性

用固相多肽合成法合成了生长激素释放肽(GHRP),这是一种含D-型氨基酸的外源性激素,具有促进脑下垂体分泌生长激素功能的人工合成六肽,其氨基酸序列为His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂.观察了使用不同剂量的GHRP对不同日龄小鼠的促生长效应,当使用最佳剂量(1000μg/kg)时,可使25日龄小鼠体重较对照组增加14.8%,同时发现鼠龄越小对GHRP越敏感,当使用剂量高达10mg/kg时仍然安全无毒.