Effect of vinconate against regional age-related changes in the gerbil brain.
We investigated age-related changes in the binding sites of muscarinic acetylcholine, forskolin, adenosine 3',5'-cyclic monophosphate (cAMP), and of a voltage-dependent L-type calcium channel blocker in the gerbil brain using receptor autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]forskolin, [3H]cAMP, and [3H]PN200-110 were used to label muscarinic receptors, adenylate cyclase, cAMP-dependent protein kinase, and L-type calcium channels, respectively. In middle-aged animals (16-month-old gerbils), [3H]QNB, [3H]PN200-110, [3H]forskolin, and [3H]cAMP binding sites were elevated in the hippocampal region compared with that of young gerbils (4 weeks old). Further, a significant elevation in [3H]forskolin binding was seen in the nucleus accumbens. In contrast, [3H]QNB, [3H]PN200-110, and [3H]forskolin binding sites were reduced in the cerebellum, neocortex and thalamus, and hypothalamus in middle-aged animals, respectively. [3H]cAMP binding was not altered in other regions except for an elevation in the hippocampus. Thus, the age-related alterations in receptor binding may proceed by different mechanisms in various brain regions. Chronic vinconate treatment partly modulated the age-related alterations in [3H]QNB, [3H]forskolin, and [3H]cAMP binding in the hippocampus, but not that of [3H]PN200-110. Vinconate also regulated the age-related changes in [3H]forskolin binding in the nucleus accumbens. These results indicate that the age-related alterations in the binding sites of muscarinic acetylcholine, forskolin, cAMP, and L-type calcium channel blocker occur in particular in the hippocampus. Further, they suggest that a novel vinca alkaloid derivative, vinconate, can partly modulate age-related changes in these binding sites.
Araki
T
T
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kanai
Y
Y
Kato
H
H
Kogure
K
K
Shuto
K
K
Ishida
Y
Y
D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005849:Gerbillinae; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects; D014748:Vinca Alkaloids / Q000494:pharmacology*
D011976:Receptors, Muscarinic; D014748:Vinca Alkaloids; D005576:Colforsin; D011813:Quinuclidinyl Benzilate; C038627:vinconate; D000242:Cyclic AMP; D000109:Acetylcholine; D017275:Isradipine