Nicotine administration decreases the number of binding sites and mRNA of M1 and M2 muscarinic receptors in specific brain regions of rat neonates.
Nicotine has been shown to delay the developmental increase of muscarinic receptors in brain of rat neonates. In this study, we have examined the muscarinic receptor binding sites and corresponding messenger RNA in rat neonates, whose mothers received nicotine in the drinking water, using competition binding study and northern blot analysis. On postnatal 14th day, nicotine treatment led to a 61% reduction in the proportion of high-affinity sites for pirenzepine (M1-subtype) to total [3H]quinuclidinyl benzilate binding sites in cerebral cortex in rat neonate. Nicotine treatment also decreased that for 11-2[[2-[(diethylamino)methyl]-1-piperidinyl]-5,11-dihydro-6H-pyrido [2,3-b] [1,4] benzodiazepin-6-one (AF-DX 116) (M2-subtype) by 77% in cerebellum on postnatal 14th day. The levels of m1 and m2 muscarinic receptor messenger RNAs in the same brain regions were also decreased in the same day after nicotine treatment. On postnatal 35th day, no difference was observed in binding sites or in messenger RNA levels of the brain regions tested (cerebral cortex, midbrain, hippocampus, cerebellum and brainstem). Our results show that nicotine reduces muscarinic receptor subtypes in developing rat brain, in part, through suppression of the messenger RNA expression, but that the effects are different among brain regions and subtypes.
Zhu
J
J
Department of Pediatrics, School of Medicine, Fukui Medical University, Matsuoka, Japan.
Taniguchi
T
T
Konishi
Y
Y
Mayumi
M
M
Muramatsu
I
I
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D001667:Binding, Competitive; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D007700:Kinetics; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism*; D013379:Substrate Specificity; D014316:Tritium
D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D009538:Nicotine