Poulin P, Szot P, Dorsa D M, Pittman Q J
Neuroscience Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Eur J Pharmacol. 1995 Dec 27;294(1):29-39. doi: 10.1016/0014-2999(95)00515-3.
Rats pretreated with an intracerebroventricular (i.c.v.) injection of 10 pmol of vasopressin or vasopressin analogs, including deamino-D-vasopressin, [pGlu4,Cyt6]vasopressin, [pGlu-Asn-Cys(Cys)]Pro-Leu-Gly-NH2, des-Gly-NH9(2)-vasopressin, Pro-Leu-Gly-NH2, Pro-Arg-Gly-NH2, became markedly hyper-responsive to the motor effects, 24 h later, to a subsequent challenge dose of vasopressin, but not vasopressin-related peptides. A vasopressin V1 receptor antagonist, [d(CH2)1(5),Tyr(Me)2]vasopressin, but not the vasopressin V2 receptor antagonist, [d(CH2)1(5),Tyr(Et)2,Val4]vasopressin, or a more selective vasopressin V2 receptor antagonist, [d(CH2)1(5),D-Ile2,Ile4]vasopressin, or the oxytocin receptor antagonist, [d(CH2)1(5),Tyr(Me)2,Thr4,Orn8,Tyr-NH9(2)]vasotocin ([d(CH2)1(5),Tyr(Me)2,Thr4,Tyr-NH9(2)]OVT), blocked vasopressin and vasopressin analog-induced sensitization. Furthermore, both vasopressin V2 receptor antagonists were found to sensitize the brain to a subsequent vasopressin injection. This vasopressin V2 receptor antagonist-induced sensitization was also blocked by the vasopressin V1 receptor antagonist. Next, we wanted to determine if this sensitization process could involve the release of endogenous vasopressin in the brain as reflected in an amplification of vasopressin mRNA expression. However pretreatment of rats with an i.c.v. vasopressin injection was not associated with an increase in vasopressin mRNA expression in the bed nucleus of the stria terminalis, medial amygdala or the paraventricular nucleus of the hypothalamus when measured 0, 1, 3, 7, 12, or 24 h after the first vasopressin injection. As many vasopressin analogs can induce sensitization, we suggest that a novel type of receptor may be involved in the sensitization process.
经脑室内（i.c.v.）注射10皮摩尔血管加压素或血管加压素类似物（包括去氨基-D-血管加压素、[pGlu4,Cyt6]血管加压素、[pGlu-Asn-Cys(Cys)]Pro-Leu-Gly-NH2、去-Gly-NH9(2)-血管加压素、Pro-Leu-Gly-NH2、Pro-Arg-Gly-NH2）预处理的大鼠，24小时后对随后注射的血管加压素的运动效应变得明显反应过度，但对血管加压素相关肽则无此反应。血管加压素V1受体拮抗剂[d(CH2)1(5),Tyr(Me)2]血管加压素可阻断血管加压素和血管加压素类似物诱导的致敏作用，而血管加压素V2受体拮抗剂[d(CH2)1(5),Tyr(Et)2,Val4]血管加压素、更具选择性的血管加压素V2受体拮抗剂[d(CH2)1(5),D-Ile2,Ile4]血管加压素或催产素受体拮抗剂[d(CH2)1(5),Tyr(Me)2,Thr4,Orn8,Tyr-NH9(2)]血管收缩素（[d(CH2)1(5),Tyr(Me)2,Thr4,Tyr-NH9(2)]OVT）则不能。此外，发现两种血管加压素V2受体拮抗剂均可使大脑对随后注射的血管加压素敏感化。血管加压素V1受体拮抗剂也可阻断这种由血管加压素V2受体拮抗剂诱导的敏感化作用。接下来，我们想确定这种敏感化过程是否可能涉及大脑中内源性血管加压素的释放，这可通过血管加压素mRNA表达的增强来反映。然而，在首次注射血管加压素后0、1、3、7、12或24小时进行测量时，经i.c.v.注射血管加压素预处理的大鼠，其终纹床核、内侧杏仁核或下丘脑室旁核中的血管加压素mRNA表达并未增加。由于许多血管加压素类似物均可诱导敏感化，我们认为一种新型受体可能参与了敏感化过程。
