The effects of isatin (indole-2, 3-dione) on pituitary adenylate cyclase-activating polypeptide-induced hyperthermia in rats.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Pataki
Imre
I
Hungarian Academy of Sciences Neurohumoral Research Group, Department of Pathophysiology, University of Szeged, Semmelweis u, 1, Szeged, Hungary. pataki@patph.szote.u-szeged.hu
Adamik
Agnes
A
Glover
Vivette
V
Tóth
Gábor
G
Telegdy
Gyula
G
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005334:Fever / Q000139:chemically induced* / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007510:Isatin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D007510:Isatin