Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats
Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats
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DOI：
10.1111/bph.12613
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发表时间：
2014-06-01
影响因子：
7.3
通讯作者：
McGregor, I. S.
中科院分区：
文献类型：
--
作者：
Hicks, C.;Ramos, L.;McGregor, I. S.
背景与目的目前人们对催产素（OT）作为一种可能的治疗精神疾病的药物很感兴趣。然而，OT的作用可能受到外周自主神经作用的限制，这可能涉及到OT和抗利尿激素V-1A受体的作用。在这里，我们在大鼠中表征了OT、抗利尿激素（AVP）和非肽OT受体激动剂WAY 267,464的心血管和体温调节作用，并评估了OT和V-1A受体在这些作用中的相对参与程度。实验方法：采用生物遥测法测定自由活动雄性Wistar大鼠OT后体温和心率(0.01 ~ 1mg kg(-1)；i.p.), AVP (0.001 - 0.1mg kg(-1)；i.p.)或WAY 267,464(10和100mg kg(-1)；i.p)。研究了OT受体拮抗剂Compound 25 （C25、5和10mg kg(-1)）和V-1A受体拮抗剂SR49059（1和10mg kg(-1)）的作用，以及WAY 267,464可能的V-1A受体拮抗剂作用。sot和AVP具有剂量依赖性，可降低体温和心率。WAY 267,464也有类似的效果，但效果更温和。SR49059对OT和AVP所致的低温和心动过缓有明显的预防作用，而C25无明显的预防作用。WAY 267,464 （100mgkg(-1)）阻止了OT的影响，并在一定程度上阻止了AVP的影响。结论和意义外周给药OT和AVP具有深远的心血管和体温调节作用，似乎主要涉及V-1A受体而不是OT受体。此外，WAY 267,464不是一种简单的OT受体激动剂，因为它具有功能相关的V-1A拮抗剂作用。
Background and PurposeThere is current interest in oxytocin (OT) as a possible therapeutic in psychiatric disorders. However, the usefulness of OT may be constrained by peripheral autonomic effects, which may involve an action at both OT and vasopressin V-1A receptors. Here, we characterized the cardiovascular and thermoregulatory effects of OT, vasopressin (AVP) and the non-peptide OT receptor agonist WAY 267,464 in rats, and assessed the relative involvement of the OT and V-1A receptors in these effects.Experimental ApproachBiotelemetry in freely moving male Wistar rats was used to examine body temperature and heart rate after OT (0.01 - 1mg kg(-1); i.p.), AVP (0.001 - 0.1mg kg(-1); i.p.) or WAY 267,464 (10 and 100mg kg(-1); i.p.). The actions of the OT receptor antagonist Compound 25 (C25, 5 and 10mg kg(-1)) and V-1A receptor antagonist SR49059 (1 and 10mg kg(-1)) were studied, as well as possible V-1A receptor antagonist effects of WAY 267,464.Key ResultsOT and AVP dose-dependently reduced body temperature and heart rate. WAY 267,464 had similar, but more modest, effects. SR49059, but not C25, prevented the hypothermia and bradycardia induced by OT and AVP. WAY 267,464 (100mgkg(-1)) prevented the effects of OT, and to some extent AVP.Conclusions and ImplicationsPeripherally administered OT and AVP have profound cardiovascular and thermoregulatory effects that appear to principally involve the V-1A receptor rather than the OT receptor. Additionally, WAY 267,464 is not a simple OT receptor agonist, as it has functionally relevant V-1A antagonist actions.