Expression and Biological Activity of B1 Bradykinin Receptors in the Hippocampus of Kindled Rats.
Abstract number :
A.04
Submission category :
Year :
2001
Submission ID :
2325
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
M. Simonato, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy; R. Couture, Department of Physiology, Faculty of Medicine, University of Montreal, Montreal, QC, Canada; G. Bregola, Department of Clinical and Experimen
RATIONALE: In the kindling model of epilepsy, a lasting hyperexcitability develops in a previously healthy brain. Increased expression of receptors mediating excitatory effects may be involved in this hyperexcitability. In this study, we tested whether B1 bradykinin receptors (which are known to mediate excitatory effects in the peripheral nervous system and have little constitutive expression in the central nervous system) may be proposed in this role.
METHODS: In sham operated control rats, 125I-HPP-Des-Arg10-Hoe 140 (150 pM, B1 receptor antagonist) binding sites were not detected in the hippocampus or in other brain areas using an autoradiographic approach. However, in fully kindled rats, 7 days after the last stimulus-evokes seizure, B1 receptor labeling was measured in the hippocampus (CA1, CA2 and CA3). Consistent with these data, electrically-evoked endogenous glutamate release from the hippocampus was unaffected by the endogenous B1 receptor agonist Lys-des-Arg9-bradykinin (10-7 M) in slices taken from control animals, but was significantly increased in slices taken from kindled rats (+50%). This effect was fully prevented by the selective B1 receptor antagonist R-715 (10-6 M), but not by the selective B2 receptor antagonist Hoe 140 (10-6 M).
CONCLUSIONS: The present data suggest that increased expression of B1 bradykinin receptors play a role in kindling hyperexcitability and, thus, may represent a new molecular target for the treatment of some forms of epilepsy.