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Workshop 2: Labeled nicotine binding in brain
447
77EFFECT
OF FETAL NICOTINE EXPOSURE ON POST-NATAL DEVELOPMFNT OF THE AUTmOMIC NERVOUS SYSTEM (ANS). G. Miller Jonakait, D. Straka and I.B. Black, Div. of Developmental Neurology, Cornell University Medical College, New York, N.Y., USA. The normal post-natal developmental increase of catecholamine-specificenzyme activity in both adrenal medulla and superior cervical ganglion (SCG) is regulated transsynaptically by transmission at nicotinic synapses. To investigate the effects of fetal nicotine exposure on the post-natal development of the ANS, pregnant rats were treated daily during gestation with 1-2 mg/kg nicotine, which is known to cross the placenta. Saline-treated rats served as controls. Pups exposed to nicotine throughout gestation had significantly lower weights at birth and throughout the developmental period. In the neonatal adrenal medulla, enzyme activity of both phenylethanolamineN-methyltransferase (PNMT) and tyrosine hydroxylase (T-OH) were significantly depressed, though deficits in INMT activity had returned to normal after the first post-natal week. By contrast, T-OH and INMT activity in the SCG was normal at all post-natal ages examined. Choline acetyltransferaseactivity, measured as an index of preganglionic terminal maturation in the SCG, was also normal in tie neonate. To test the effect of pre-natal nicotine exposure on adult ANS responsiveness,animals exposed to nicotine during gestation were treated with nicotine as adults. Control animals showed an expected 42% increase in ganglionic T-OH activity. However, the adult response to nicotine was lacking in animals exposed pre-natally to nicotine.
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WORKSHOP 2: LABELED NICOTINE BINDING IN BRAIN Henry Sershen Center for Neurochemistry,Ward's Island, New York, NY
10035
This presentation will discuss recent studies on the properties of labeled nicotine binding in brain and the possibility that a specific noncholinergic recep or in brain mediates the central effects of nicotine. Scatchard nicotine binding to neural membranes indicates analysis of [ $HInicotine multiple binding sites with Rd’s of l-100 nM for the high-affinity site and a low-affinity uM site. Comparison of labeled nicotine, acetylcholine, and bungarotoxin binding in brain suggests that these sites are different, although overlap occurs. Up-regulation of the acetylcholine and nicotine binding site was observed in adult animals after chronic treatment with nicotine; we observed a similar increase in nicotine binding in the offspring of rats treated during gestation with nicotine. We have found in brain extract material that inhibits nicotine and acetylcholine binding. partially purified material (possibly peptide) also inhibits [3H]D-Ala,DTtit enkephalin binding. Competition studies indicate that a portion of nicotine binding is not inhibited by acetylcholine. These results together with regional distribution studies with labeled nicotine and acetylcholine suggests that a portion of nicotine binding is to noncholinergic sites. Supported by CPR, Inc., USA.
79RFFECTS OF NICOTINR ON RLASTOCYNT DEVELOPMRNT PRIOR TO IMPLANTATION IN THE RAT. 'J.A.MitcbcJL and R.E. Hcumper,Department of Anatomy, Wayne State University, School of ) FE, 8.38” Medicine , Detrcbit ’ Twice daily sc injection (5 mg/kg) of nicotine (N) during the first 5 days of pregnancy in the rat retards blastocyst growth as indicated by the reduced number of cells per blastocyst in N vs. saline (24)treated rats (N: 22.2+2.7 vs S: 42.0+3.2 cells; p
2
77EFFECT
OF FETAL NICOTINE EXPOSURE ON POST-NATAL DEVELOPMFNT OF THE AUTmOMIC NERVOUS SYSTEM (ANS). G. Miller Jonakait, D. Straka and I.B. Black, Div. of Developmental Neurology, Cornell University Medical College, New York, N.Y., USA. The normal post-natal developmental increase of catecholamine-specificenzyme activity in both adrenal medulla and superior cervical ganglion (SCG) is regulated transsynaptically by transmission at nicotinic synapses. To investigate the effects of fetal nicotine exposure on the post-natal development of the ANS, pregnant rats were treated daily during gestation with 1-2 mg/kg nicotine, which is known to cross the placenta. Saline-treated rats served as controls. Pups exposed to nicotine throughout gestation had significantly lower weights at birth and throughout the developmental period. In the neonatal adrenal medulla, enzyme activity of both phenylethanolamineN-methyltransferase (PNMT) and tyrosine hydroxylase (T-OH) were significantly depressed, though deficits in INMT activity had returned to normal after the first post-natal week. By contrast, T-OH and INMT activity in the SCG was normal at all post-natal ages examined. Choline acetyltransferaseactivity, measured as an index of preganglionic terminal maturation in the SCG, was also normal in tie neonate. To test the effect of pre-natal nicotine exposure on adult ANS responsiveness,animals exposed to nicotine during gestation were treated with nicotine as adults. Control animals showed an expected 42% increase in ganglionic T-OH activity. However, the adult response to nicotine was lacking in animals exposed pre-natally to nicotine.
78
WORKSHOP 2: LABELED NICOTINE BINDING IN BRAIN Henry Sershen Center for Neurochemistry,Ward's Island, New York, NY
10035
This presentation will discuss recent studies on the properties of labeled nicotine binding in brain and the possibility that a specific noncholinergic recep or in brain mediates the central effects of nicotine. Scatchard nicotine binding to neural membranes indicates analysis of [ $HInicotine multiple binding sites with Rd’s of l-100 nM for the high-affinity site and a low-affinity uM site. Comparison of labeled nicotine, acetylcholine, and bungarotoxin binding in brain suggests that these sites are different, although overlap occurs. Up-regulation of the acetylcholine and nicotine binding site was observed in adult animals after chronic treatment with nicotine; we observed a similar increase in nicotine binding in the offspring of rats treated during gestation with nicotine. We have found in brain extract material that inhibits nicotine and acetylcholine binding. partially purified material (possibly peptide) also inhibits [3H]D-Ala,DTtit enkephalin binding. Competition studies indicate that a portion of nicotine binding is not inhibited by acetylcholine. These results together with regional distribution studies with labeled nicotine and acetylcholine suggests that a portion of nicotine binding is to noncholinergic sites. Supported by CPR, Inc., USA.
79RFFECTS OF NICOTINR ON RLASTOCYNT DEVELOPMRNT PRIOR TO IMPLANTATION IN THE RAT. 'J.A.MitcbcJL and R.E. Hcumper,Department of Anatomy, Wayne State University, School of ) FE, 8.38” Medicine , Detrcbit ’ Twice daily sc injection (5 mg/kg) of nicotine (N) during the first 5 days of pregnancy in the rat retards blastocyst growth as indicated by the reduced number of cells per blastocyst in N vs. saline (24)treated rats (N: 22.2+2.7 vs S: 42.0+3.2 cells; p
2