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

Pataki I, Adamik A, Glover V, Tóth G, Telegdy G - BMC Neurosci (2002)

Bottom Line: Isatin (indole-2, 3-dione) is an endogenous indole that has previously been found to inhibit hyperthermic effects of natriuretic peptides.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hungarian Academy of Sciences Neurohumoral Research Group, Department of Pathophysiology, University of Szeged, Semmelweis u, 1, Szeged, Hungary. pataki@patph.szote.u-szeged.hu

ABSTRACT

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.

Conclusion: 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.

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Effects of isatin on PACAP-38-induced hyperthermia. Groups of rats received an i.p. injection of saline (PACAP 1 μg group) or different doses (12.5, 18.75, 25 or 50 mg/kg) of isatin (Isa. + PACAP groups) 3.5 h after an i.c.v. injection of 1 μg PACAP-38. The control group received an i.p. saline injection 3.5 h after i.c.v. saline treatment (groups of animals receiving different dilutions (12.5, 18.75, 25 or 50 mg/kg; i.p.) of isatin 3.5 h after an i.c.v. saline injection are not shown). Number of animals per group is presented in parentheses after the corresponding group. The vertical lines on the top of the marks denote the S.E.M. The vertical arrow denotes the time of isatin injection (3.5 h). * p < 0.05 PACAP vs. other groups; × p < 0.05 control vs. other groups; ** p < 0.05 Isa. 18.75 + PACAP compared with the control, the Isa. 25 + PACAP, the Isa. 50 + PACAP and with the PACAP 1 μg groups.
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Figure 1: Effects of isatin on PACAP-38-induced hyperthermia. Groups of rats received an i.p. injection of saline (PACAP 1 μg group) or different doses (12.5, 18.75, 25 or 50 mg/kg) of isatin (Isa. + PACAP groups) 3.5 h after an i.c.v. injection of 1 μg PACAP-38. The control group received an i.p. saline injection 3.5 h after i.c.v. saline treatment (groups of animals receiving different dilutions (12.5, 18.75, 25 or 50 mg/kg; i.p.) of isatin 3.5 h after an i.c.v. saline injection are not shown). Number of animals per group is presented in parentheses after the corresponding group. The vertical lines on the top of the marks denote the S.E.M. The vertical arrow denotes the time of isatin injection (3.5 h). * p < 0.05 PACAP vs. other groups; × p < 0.05 control vs. other groups; ** p < 0.05 Isa. 18.75 + PACAP compared with the control, the Isa. 25 + PACAP, the Isa. 50 + PACAP and with the PACAP 1 μg groups.

Mentions: I.c.v. administration of PACAP-38 (1 μg) elevated the colon temperature 2, 3, 4, 5 and 6 h after administration. These observations were in accordance with our previously published data [5]. An I.p. injection of different doses of isatin (18.75, 25 and 50 mg/kg) 3.5 h after peptide treatment significantly diminished the hyperthermia in PACAP-38-treated animals at 4 and 5 h in a dose-dependent manner [F (9, 97)2,3,4,5,6 h = 3.75, 24.26, 22.71, 24.91, 20.21; p < 0.05]. Isatin had no antihyperthermic effect at 6 h (Fig. 1). Control injections of isatin (12.5, 18.75, 25 and 50 mg/kg; i.p.) 3.5 h after i.c.v. saline administration did not modify the colon temperature (data not shown).


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

Pataki I, Adamik A, Glover V, Tóth G, Telegdy G - BMC Neurosci (2002)

Effects of isatin on PACAP-38-induced hyperthermia. Groups of rats received an i.p. injection of saline (PACAP 1 μg group) or different doses (12.5, 18.75, 25 or 50 mg/kg) of isatin (Isa. + PACAP groups) 3.5 h after an i.c.v. injection of 1 μg PACAP-38. The control group received an i.p. saline injection 3.5 h after i.c.v. saline treatment (groups of animals receiving different dilutions (12.5, 18.75, 25 or 50 mg/kg; i.p.) of isatin 3.5 h after an i.c.v. saline injection are not shown). Number of animals per group is presented in parentheses after the corresponding group. The vertical lines on the top of the marks denote the S.E.M. The vertical arrow denotes the time of isatin injection (3.5 h). * p < 0.05 PACAP vs. other groups; × p < 0.05 control vs. other groups; ** p < 0.05 Isa. 18.75 + PACAP compared with the control, the Isa. 25 + PACAP, the Isa. 50 + PACAP and with the PACAP 1 μg groups.
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Related In: Results  -  Collection

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Figure 1: Effects of isatin on PACAP-38-induced hyperthermia. Groups of rats received an i.p. injection of saline (PACAP 1 μg group) or different doses (12.5, 18.75, 25 or 50 mg/kg) of isatin (Isa. + PACAP groups) 3.5 h after an i.c.v. injection of 1 μg PACAP-38. The control group received an i.p. saline injection 3.5 h after i.c.v. saline treatment (groups of animals receiving different dilutions (12.5, 18.75, 25 or 50 mg/kg; i.p.) of isatin 3.5 h after an i.c.v. saline injection are not shown). Number of animals per group is presented in parentheses after the corresponding group. The vertical lines on the top of the marks denote the S.E.M. The vertical arrow denotes the time of isatin injection (3.5 h). * p < 0.05 PACAP vs. other groups; × p < 0.05 control vs. other groups; ** p < 0.05 Isa. 18.75 + PACAP compared with the control, the Isa. 25 + PACAP, the Isa. 50 + PACAP and with the PACAP 1 μg groups.
Mentions: I.c.v. administration of PACAP-38 (1 μg) elevated the colon temperature 2, 3, 4, 5 and 6 h after administration. These observations were in accordance with our previously published data [5]. An I.p. injection of different doses of isatin (18.75, 25 and 50 mg/kg) 3.5 h after peptide treatment significantly diminished the hyperthermia in PACAP-38-treated animals at 4 and 5 h in a dose-dependent manner [F (9, 97)2,3,4,5,6 h = 3.75, 24.26, 22.71, 24.91, 20.21; p < 0.05]. Isatin had no antihyperthermic effect at 6 h (Fig. 1). Control injections of isatin (12.5, 18.75, 25 and 50 mg/kg; i.p.) 3.5 h after i.c.v. saline administration did not modify the colon temperature (data not shown).

Bottom Line: Isatin (indole-2, 3-dione) is an endogenous indole that has previously been found to inhibit hyperthermic effects of natriuretic peptides.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hungarian Academy of Sciences Neurohumoral Research Group, Department of Pathophysiology, University of Szeged, Semmelweis u, 1, Szeged, Hungary. pataki@patph.szote.u-szeged.hu

ABSTRACT

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.

Conclusion: 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.

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