Torres B A, Johnson H M
Department of Comparative and Experimental Pathology, University of Florida, Gainesville 32610.
J Immunol. 1988 Apr 1;140(7):2179-83.
Arginine vasopressin (AVP), a nine-amino acid neurohypophyseal hormone, is capable of replacing the helper cell requirement for IFN-gamma production by Lyt-2+ mouse splenic lymphocytes. We present data here showing that the AVP helper signal occurs via interaction with a novel R on splenic lymphocytes and involves primarily the N-terminal six-amino acid cyclic ring (pressinoic acid) with the C-terminal three-amino acid end of AVP playing a minor role. Pressinoic acid was capable of providing help at concentrations similar to those of AVP, whereas oxytocin and isoleucine pressinoic acid were 10- and 100-fold less effective, respectively. Isoleucine pressinoic acid has the same structure as pressinoic acid except for the substitution of isoleucine for phenylalanine in position 3 of the sequence. Consistent with the function data, R binding competitions with splenic lymphocyte membrane preparations showed that AVP and pressinoic acid competed similarly with [3H]AVP, whereas oxytocin and isoleucine pressinoic acid were much less effective competitors. Further characterization of the AVP lymphocyte R was performed using AVP analogues having well defined agonist and antagonist activities on either V1 (vasopressor) R or V2 (antidiuretic) R. The AVP helper signal was blocked by the V1 antagonist [d(CH2)1(5) Tyr(methyl)]AVP but not by another V1 antagonist, [d(CH2)1(5)D-Tyr(ethyl)2Val4]AVP. Both V1-R antagonists were able to block [3H]AVP binding to the V1-R on liver cells, whereas only the V1 antagonist that blocked AVP help was able to compete effectively for the spleen AVP-R. Neither a V2 agonist nor a V2 antagonist had any effect on AVP help in IFN-gamma production. These data strongly indicate the presence of a novel AVP-R on spleen lymphocytes, which is related to the classic V1-R on liver cell membranes.
精氨酸加压素（AVP）是一种由九个氨基酸组成的神经垂体激素，能够替代辅助细胞，使Lyt-2⁺小鼠脾淋巴细胞产生γ干扰素。我们在此展示的数据表明，AVP辅助信号通过与脾淋巴细胞上一种新的R相互作用产生，主要涉及N端六个氨基酸的环状结构（加压素酸），而AVP的C端三个氨基酸末端起次要作用。加压素酸能够在与AVP相似的浓度下提供辅助作用，而催产素和异亮氨酸加压素酸的效力分别低10倍和100倍。异亮氨酸加压素酸与加压素酸结构相同，只是在序列的第3位用异亮氨酸取代了苯丙氨酸。与功能数据一致，脾淋巴细胞膜制剂的R结合竞争实验表明，AVP和加压素酸与[³H]AVP的竞争情况相似，而催产素和异亮氨酸加压素酸作为竞争者的效力则低得多。使用对V1（血管升压素）R或V2（抗利尿）R具有明确激动剂和拮抗剂活性的AVP类似物，对AVP淋巴细胞R进行了进一步表征。AVP辅助信号被V1拮抗剂[d(CH₂)₁₅Tyr(甲基)]AVP阻断，但未被另一种V1拮抗剂[d(CH₂)₁₅D-Tyr(乙基)₂Val₄]AVP阻断。两种V1-R拮抗剂都能够阻断[³H]AVP与肝细胞上V1-R的结合，而只有阻断AVP辅助作用的V1拮抗剂能够有效竞争脾AVP-R。V2激动剂和V2拮抗剂对γ干扰素产生过程中AVP的辅助作用均无影响。这些数据有力地表明，脾淋巴细胞上存在一种新的AVP-R，它与肝细胞膜上的经典V1-R相关。
