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三种新型精氨酸加压素(AVP)类似物(丙氨酸-AVP、丝氨酸-丙氨酸-AVP、苏氨酸-丝氨酸-丙氨酸-AVP)对离体大鼠尾动脉的收缩活性与单独使用AVP的关系。

Constrictory activity of three new arginine-vasopressin (AVP) analogues (Ala-AVP, Ser-Ala-AVP, Thr-Ser-Ala-AVP) towards isolated rat tail artery as related to AVP alone.

作者信息

Kalïszan R, Petrusewicz J, Juzwa W, Rekowski P, Lammek B, Kupryszewski G

机构信息

Biopharmaceutics and Pharmacodynamics Unit, Medical Academy, Gdańsk, Poland.

出版信息

Pharmacol Res Commun. 1988 May;20(5):377-81. doi: 10.1016/s0031-6989(88)80013-4.

Abstract

The constrictory activity of vasopressin and its three novel analogues extended by 1-3 amino acids in accordance with the sequence of the bovine arginine-vasopressin neurophysin II precursor has been studied on isolated rat tail artery preparation. The analogues showed lower constrictory potency than AVP, but these agents strongly interacted with AVP. The net effect of interactions appeared complex and dependent on the nature and concentrations of the interacting agents. Basing on recent findings (Land et al. 1982) concerning the sequence of the bovine arginine-vasopressin neurophysin II precursor, Lammek et al. (1987) synthesized vasopressin analogues with primary structures derived from this precursor. Three such analogues, Ala-AVP, Ser-Ala-AVP, and Thr-Ser-Ala-AVP, showed pressor activity (147, 109, and 86 international units/mumol respectively) and antidiuretic activity (52, 130, and 48 international units/mumol, respectively) after intravenous administration to rats (Lammek et al. 1987). Having in view the possible clinical applications of vasopressin analogues and hormonogens in the treatment of bleeding disorders we were interested in the direct effect of the agents on isolated blood vessels. As the analogues considered may theoretically appear in a living system and interact with the native AVP, such interaction on the isolated rat tail artery preparation was analysed.

摘要

根据牛精氨酸加压素神经垂体素II前体的序列,将加压素及其三种新类似物(通过1 - 3个氨基酸进行延伸)的收缩活性在离体大鼠尾动脉标本上进行了研究。这些类似物的收缩效力低于AVP,但这些药物与AVP有强烈的相互作用。相互作用的净效应显得复杂,且取决于相互作用药物的性质和浓度。基于最近关于牛精氨酸加压素神经垂体素II前体序列的研究结果(Land等人,1982年),Lammek等人(1987年)合成了具有源于该前体一级结构的加压素类似物。给大鼠静脉注射后,三种这样的类似物,即丙氨酸 - AVP、丝氨酸 - 丙氨酸 - AVP和苏氨酸 - 丝氨酸 - 丙氨酸 - AVP,分别显示出升压活性(分别为147、109和86国际单位/微摩尔)和抗利尿活性(分别为52、130和48国际单位/微摩尔)(Lammek等人,1987年)。鉴于加压素类似物和激素原在治疗出血性疾病方面可能的临床应用,我们对这些药物对离体血管的直接作用感兴趣。由于所考虑的类似物理论上可能出现在生物系统中并与天然AVP相互作用,因此对离体大鼠尾动脉标本上的这种相互作用进行了分析。

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