[Involvements of neuropeptides in pentylenetetrazol-induced convulsion in rats and effects of TRH and ceruletide on the convulsion].
To study the possible involvements of neuropeptides in the occurrence of convulsion, pentylenetetrazol (PTZ) was given to male Wistar rats weighing 250-350 g, and the concentration of neurotensin (NT), and the maximal number of binding sites (Bmax) and dissociation constant (Kd) of NT receptor in the frontal cortex were measured. The effect of the pretreatment of thyrotropin-releasing hormone (TRH) or ceruletide (CER) on the convulsion was also studied. NT was extracted from the homogenates of rat frontal cortex by boiling, and measured by radioimmunoassay. Membrane fractions were incubated with increasing concentrations of 125I-NT. Nonspecific binding was determined in the presence of unlabeled NT and subtracted from total binding to obtain the specific binding. The Bmax and Kd were calculated by Scatchard analysis. Generalized convulsion appeared after intraperitoneal administration of 50 mg/kg PTZ with a latency of 68.2 +/- 4.4 sec. One hour after the administration, neurotensin-like immunoreactivity (NTLI) concentration was reduced from 4.7 +/- 0.6 to 2.3 +/- 0.1 ng/g wet wt (p less than 0.01) and the Bmax of NT receptor from 17.2 +/- 2.8 to 10.8 +/- 1.1 fmol/mg protein (p less than 0.01). However no significant changes were observed in somatostatin-like immunoreactivity (SSLI) concentration and the Bmax and Kd of SS receptor. These facts indicate that PTZ stimulates the release of NT resulting in down regulation of NT receptor. Pretreatment with intracerebroventricular (icv) administration of 30 micrograms/10 microliters NT 30 min before the 50 mg/kg PTZ administration shortened the duration of the convulsion from 135.0 +/- 42.8 to 11.5 +/- 11.9 sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Hashiguchi
S
S
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Masuda
T
T
Fujimoto
H
H
Kawai
H
H
Saito
S
S
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002108:Ceruletide / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017481:Receptors, Somatostatin; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D009479:Neuropeptides; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D009496:Neurotensin; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D002108:Ceruletide; D010433:Pentylenetetrazole