Abnormality of alpha 1-adrenergic receptors in the frontal cortex of epileptic rats.
We found that the binding of [3H]prazosin, a selective ligand for alpha 1-adrenergic recognition sites, is significantly lower in the frontal cortex of the genetically epilepsy-prone rats (GEPRs), as compared with normal Sprague-Dawley rats. Scatchard analysis reveals a decrease in the Bmax of [3H]prazosin binding with no change in the apparent KD, suggesting that there are fewer alpha 1-adrenergic recognition sites in the frontal cortex of the GEPR. This abnormality is associated with a reduced capacity of norepinephrine (NE) to stimulate [3H]inositol monophosphate ([3H]IP1) formation in frontal cortex slices prelabeled with [3H]inositol. No significant differences in [3H]prazosin binding as well as NE-stimulated [3H]IP1 formation have been observed in other brain regions including hippocampus, corpus striatum, and inferior colliculus. These results indicate that a deficit in the alpha 1-adrenergic receptor system in the frontal cortex may play a role in the seizure process in the GEPR.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D003000:Clonidine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D006624:Hippocampus / Q000378:metabolism; D007245:Inferior Colliculi / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism / Q000502:physiology*; D013570:Synaptic Membranes / Q000378:metabolism; D015016:Yohimbine / Q000378:metabolism
D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D002217:Carbachol; D011433:Propranolol; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine