High-affinity choline transport regulation by drug administration during postnatal development.
High-affinity choline transport sites specifically bind [3H]hemicholinium-3. Hemicholinium-3 binding sites are regulated by in vivo drug treatments in the same manner as these drugs alter acetylcholine release and high-affinity choline transport. The current study examines regulation of binding sites by in vivo drug administration for adult, day 15, and day 5 rats. Drugs or saline were administered intraperitoneally, and striatal and cortical membrane preparations were assayed. Control [3H]hemicholinium-3 binding increases twofold between postnatal days 5 and 15 only in striatum. After day 15, binding increases 2.7-fold in cortex and striatum. Nicotine treatment increases striatal and cortical hemicholinium-3 binding at all three ages, with greater percent increases at day 5. Haloperidol increases binding only in striatum, again with larger effects at day 5. Both striatal and cortical binding are reduced by oxotremorine; however, the magnitude of this effect is unchanged during development. Pentobarbital reduces binding only in striatum, with no developmental change. Atropine and apomorphine do not change binding from control values. In summary, all drug treatments effective in adults were already effective by day 5. Cholinergic terminals present early in development are regulated by similar nicotinic and muscarinic cholinergic, dopaminergic, and sedative-hypnotic mechanisms as the adult. Changes in magnitude may be due to changes in drug metabolism or to developmental differences in regulation.
Happe
H K
HK
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260.
Murrin
L C
LC
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology; D002794:Choline / Q000378:metabolism / Q000493:pharmacokinetics*; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D006426:Hemicholinium 3 / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D010424:Pentobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D049590:Postpartum Period; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D014316:Tritium; D006426:Hemicholinium 3; D009538:Nicotine; D010424:Pentobarbital; D006220:Haloperidol; D002794:Choline