Changes in hippocampal and cortical B1 bradykinin receptor biological activity in two experimental models of epilepsy.
An increased response to the activation of receptors mediating excitatory effects may be involved in some forms of epilepsy. In this study, it has been tested whether B1 bradykinin receptors (which mediate excitatory effects in the peripheral nervous system and have little constitutional expression in the central nervous system) may be proposed in this role. Two experimental models of epilepsy (kindling and kainate) have been employed, and glutamate outflow experiments have been performed in hippocampal and cortical slices taken from control, kindled and kainate-treated rats. The endogenous B1 receptor agonist Lys-des-Arg9-bradykinin (10(-7) M) did not affect electrically-evoked glutamate overflow in control animals, but concentration-dependently increased it in kindled rats (maximal effect +40 to + 50%) and, to a lesser extent (+20%), in kainate-treated rats. These effects were 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). The observed changes in B1 bradykinin receptor biological activity may play a role in epileptic hyperexcitability.
Bregola
G
G
Department of Clinical and Experimental Medicine, University of Ferrara, Italy.
Varani
K
K
Gessi
S
S
Beani
L
L
Bianchi
C
C
Borea
P A
PA
Regoli
D
D
Simonato
M
M
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002540:Cerebral Cortex / Q000378:metabolism*; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid; D007609:Kallidin / Q000031:analogs & derivatives / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*
D065168:Bradykinin Receptor Antagonists; C120984:R 715; D018002:Receptors, Bradykinin; D007609:Kallidin; D018698:Glutamic Acid; C052787:kallidin, des-Arg(10)-; C065679:icatibant; D001920:Bradykinin; D007608:Kainic Acid