Altered postnatal ontogeny of alpha 1- and alpha 2-adrenoceptor binding sites in the brain of a convulsive mutant mouse (quaking).
Binding assays of [3H]dihydroalprenolol ([3H]DHA), [3H]prazosin and [3H]clonidine have been performed on whole brain (minus cerebellum) homogenates of the convulsive mutant mice quaking (qk) and the controls of the same strain (C57BL/6J:B6). In 70-day-old mutants (which fully exhibit the qk convulsive phenotype), the binding of [3H]DHA to beta-adrenoceptor binding sites was not different from the controls, whereas the binding capacities of [3H]prazosin and [3H]clonidine to alpha 1-and alpha 2-adrenoceptor sites, respectively, were greatly enhanced. The biphasic ontogenic pattern of alpha 2-adrenoceptors had a greater amplitude in the brain of 30- to 90-day-old mutants than in the corresponding B6 controls. In mutants younger than 30 days or older than 90 days, the number of alpha 2-adrenoceptor sites was not modified. The number of alpha 1-adrenoceptor binding sites was increased in the brain of the mutants, only in animals older than 70 days. In younger mice, the postnatal modulation of alpha 1-adrenoceptor sites was identical to the controls. Regional studies were performed in 70-day-old mice. [3H]clonidine binding was increased in the brainstem of the mutants, and to a lesser extent in the cerebral cortex, while it was slightly diminished in the hypothalamic area. [3H]prazosin binding was also increased in the brainstem of the mutants, and decreased in the olfactory bulbs. Our results suggest that the convulsions of the qk mutants are selectively associated with modifications of alpha- and not beta-adrenoceptor binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001921:Brain / Q000254:growth & development; D001923:Brain Chemistry; D003000:Clonidine / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008821:Mice, Quaking; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D012640:Seizures / Q000378:metabolism* / Q000503:physiopathology
D011942:Receptors, Adrenergic, alpha; D004082:Dihydroalprenolol; D003000:Clonidine; D011224:Prazosin