Shah G V, Epand R M, Orlowski R C
Mol Cell Endocrinol. 1987 Feb;49(2-3):203-10. doi: 10.1016/0303-7207(87)90214-0.
Receptor binding assays demonstrate that bovine parathyroid hormone (PTH) and human PTH(1-34) can displace [125I]iodoglucagon from binding to its receptor in rat liver plasma membranes. The displacement of [125I]iodoglucagon requires several thousand-fold more bovine PTH or human PTH(1-34) than glucagon. However, the PTH peptides are more effective than secretin, which up to a concentration of 10(-5) M exhibits no ability to displace [125I]iodoglucagon. The greater potency of PTH compared with secretin occurs despite the fact that secretin shows a great deal of sequence homology with glucagon while PTH shows none. We demonstrate by circular dichroism that in the presence of 3 mM SDS glucagon and hPTH(1-34) have similar secondary structure contents, while secretin is more helical. Our results suggest that receptors can recognize gross conformational features of a peptide hormone in addition to interacting with a specific amino acid sequence. The ability of PTH to interact with glucagon receptors can be modulated by incorporation of charged amphiphiles into the plasma membrane. Negatively charged taurodeoxycholic acid increases the binding of the more cationic PTH while positively charged myristyltrimethylammonium bromide decreases this interaction. These effects demonstrate that receptor specificity can be modulated by its lipid environment and that electrostatic interactions between the hormone and the membrane surface can contribute to receptor binding.
受体结合试验表明，牛甲状旁腺激素（PTH）和人PTH（1-34）能在大鼠肝细胞膜中取代[125I]碘胰高血糖素与其受体的结合。取代[125I]碘胰高血糖素需要比胰高血糖素多几千倍的牛PTH或人PTH（1-34）。然而，PTH肽比促胰液素更有效，促胰液素在浓度高达10^(-5) M时没有取代[125I]碘胰高血糖素的能力。尽管促胰液素与胰高血糖素具有大量的序列同源性，而PTH则没有，但PTH的效力仍比促胰液素更强。我们通过圆二色性证明，在3 mM SDS存在的情况下，胰高血糖素和hPTH（1-34）具有相似的二级结构含量，而促胰液素的螺旋结构更多。我们的结果表明，受体除了与特定的氨基酸序列相互作用外，还能识别肽激素的总体构象特征。PTH与胰高血糖素受体相互作用的能力可通过将带电荷的两亲物掺入质膜来调节。带负电荷的牛磺脱氧胆酸增加了带更多阳离子的PTH的结合，而带正电荷的肉豆蔻基三甲基溴化铵则减少了这种相互作用。这些效应表明，受体特异性可由其脂质环境调节，并且激素与膜表面之间的静电相互作用可有助于受体结合。
