Pronounced increases in brain levels of calcitonin gene-related peptide after kainic acid induced seizures.
Changes in immunoreactivity of calcitonin gene-related peptide (CGRP) were investigated in the brains of rats subsequently to seizures induced by intraperitoneal injection of kainic acid (10 mg/kg, i.p.). Increased levels of the neuropeptide were observed in the frontal cortex (increase of 1300% of control value), striatum (900%), dorsal hippocampus (400%) and amygdala/pyriform cortex (135%) three days after injection of the neurotoxin. Intravenous infusion of mannitol (1.5 g/kg, under thiopental anesthesia) which prevents seizures and post-seizure brain damage suppressed the changes in CGRP-like immunoreactivity. Injection of pentylenetetrazol causing generalized motor seizures resulted in no change of CGRP-immunoreactivity after three days. The pronounced but reversible increases of brain CGRP levels suggest a strong but short-lasting activation of the peptide system. The failure of pentylenetetrazol to produce a similar effect and the protective action of mannitol suggest that sustained seizures and/or post-seizure brain damage may be required to produce the rise in peptide levels.
Saria
A
A
Department of Pharmacology, University of Innsbruck, Austria.
Marksteiner
J
J
Humpel
C
C
Sperk
G
G
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D008353:Mannitol; D005968:Glutamate Decarboxylase; D015740:Calcitonin Gene-Related Peptide; D007608:Kainic Acid; D010433:Pentylenetetrazole