Pataki Imre, Adamik Agnes, Glover Vivette, Tóth Gábor, Telegdy Gyula
Hungarian Academy of Sciences Neurohumoral Research Group, Department of Pathophysiology, University of Szeged, Semmelweis u, 1, Szeged, Hungary.
BMC Neurosci. 2002;3:2. doi: 10.1186/1471-2202-3-2. Epub 2002 Feb 20.
Previous studies have demonstrated that centrally administered natriuretic peptides and pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) have hyperthermic properties. Isatin (indole-2, 3-dione) is an endogenous indole that has previously been found to inhibit hyperthermic effects of natriuretic peptides. In this study the aim was to investigate the effects of isatin on thermoregulatory actions of PACAP-38, in rats.
One microg intracerebroventricular (icv.) injection of PACAP-38 had hyperthermic effect in male, Wistar rats, with an onset of the effect at 2 h and a decline by the 6th h after administration. Intraperitoneal (ip.) injection of different doses of isatin (25-50 mg/kg) significantly decreased the hyperthermic effect of 1 microg PACAP-38 (icv.), whereas 12.5 mg/kg isatin (ip.) had no inhibiting effect. Isatin alone did not modify the body temperature of the animals.
The mechanisms that participate in the mediation of the PACAP-38-induced hyperthermia may be modified by isatin. The capability of isatin to antagonize the hyperthermia induced by all members of the natriuretic peptide family and by PACAP-38 makes it unlikely to be acting directly on receptors for natriuretic peptides or on those for PACAP in these hyperthermic processes.
先前的研究表明，中枢给予利钠肽和垂体腺苷酸环化酶激活多肽-38（PACAP-38）具有升温特性。异吲哚酮（吲哚-2,3-二酮）是一种内源性吲哚，此前已发现其可抑制利钠肽的升温作用。在本研究中，目的是探讨异吲哚酮对大鼠PACAP-38体温调节作用的影响。
向雄性Wistar大鼠脑室内（icv.）注射1微克PACAP-38具有升温作用，给药后2小时开始起效，6小时后作用减弱。腹腔内（ip.）注射不同剂量的异吲哚酮（25 - 50毫克/千克）可显著降低1微克PACAP-38（icv.）的升温作用，而12.5毫克/千克异吲哚酮（ip.）则无抑制作用。单独使用异吲哚酮不会改变动物的体温。
参与介导PACAP-38诱导的体温升高的机制可能会被异吲哚酮改变。异吲哚酮拮抗利钠肽家族所有成员和PACAP-38诱导的体温升高的能力表明，在这些体温升高过程中，它不太可能直接作用于利钠肽受体或PACAP受体。
