Twery M J, Seitz P K, Nickols G A, Cooper C W, Gallagher J P, Orlowski R C
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Eur J Pharmacol. 1988 Oct 18;155(3):285-92. doi: 10.1016/0014-2999(88)90515-8.
The conformation-activity relationship of salmon calcitonin in kidney and brain was investigated with regard to effects on membrane binding and adenylate cyclase activity. Since an amphipathic alpha-helical conformation on the calcitonin molecule is associated with high potency in lowering serum calcium, the activity of the parent peptide was compared to that of [Gly8, D-Arg24]des-Leu16-salmon calcitonin, a calcitonin analogue (CTA) with less helix forming potential. The results indicate that while salmon calcitonin possesses similar potency in brain and kidney, CTA is effective only in brain. Furthermore, CTA did not inhibit the binding of 125I-labeled human calcitonin gene-related peptide (HCGRP) to brain membranes. Our findings suggest that the specific binding and effects of salmon calcitonin on adenylate cyclase activity in brain do not depend on conformational features in the middle region of the molecule, although the alpha-helical structure in this region does appear to be an important property for salmon calcitonin binding to renal cortical membranes.
就对膜结合和腺苷酸环化酶活性的影响而言，研究了鲑鱼降钙素在肾脏和大脑中的构象 - 活性关系。由于降钙素分子上的两亲性α - 螺旋构象与降低血清钙的高效能相关，因此将母体肽的活性与[甘氨酸8，D - 精氨酸24]去亮氨酸16 - 鲑鱼降钙素（一种形成螺旋潜力较小的降钙素类似物（CTA））的活性进行了比较。结果表明，虽然鲑鱼降钙素在大脑和肾脏中具有相似的效能，但CTA仅在大脑中有效。此外，CTA不抑制125I标记的人降钙素基因相关肽（HCGRP）与脑膜的结合。我们的研究结果表明，鲑鱼降钙素对大脑中腺苷酸环化酶活性的特异性结合和作用不依赖于分子中间区域的构象特征，尽管该区域的α - 螺旋结构似乎是鲑鱼降钙素与肾皮质膜结合的重要特性。
