RESUMO
The George B. Koelle Symposium on the Cholinergic Synapse described the early development of the importance of ACh as a transmitter at both cholinergic synapses of the CNS, ganglion and neuromuscular junction. While a great deal is known about the function of cholinergic transmission at the neuromuscular junction, the integrated role of cholinergic, nicotinic and muscarinic receptors in the overall process of CNS functions, i.e., behavior, motor control, abstract thinking, memory and speech remains as a challenge for future investigation. The architecture of the cholinergic synapse appears to be a dynamic process involving ARIA, Agrin and the various forms of ACh esterase. The regulation of gene expression and site directed localization of postsynaptic cholinergic receptor proteins during the life cycle involves the dynamic interactions of these agents with the postsynaptic membrane and postsynaptic gene express. The last two papers at the symposium dealt with the chemistry of the nicotinic receptor regulated channel involved in ACh binding and the consequent cationic channel conductional changes.
Assuntos
Acetilcolina/fisiologia , Fibras Colinérgicas/fisiologia , Sinapses/fisiologia , Transmissão SinápticaRESUMO
The uptake of choline into cholinergic neurons for acetylcholine (ACh) synthesis is by a specific, high-affinity, sodium- and temperature-dependent transport mechanism (HAChU). Of several quaternary quinuclidinol derivatives tested, the N-allyl derivative proved to be most potent. Though the methyl, ethyl, and isopropyl derivatives were less potent at comparable concentrations, at higher concentrations they also maximally inhibited HAChU. The benzyl, hydroxyethyl, and methoxyethyl derivatives failed to inhibit HAChU by greater than 50% at concentrations up to 100 microM. N-Allyl-3-quinuclidinol (NAQ) proved to be a specific inhibitor of HAChU (IC50 = 0.9 microM) and a poor inhibitor of both sodium-independent transport (IC50 = 680 microM) and choline acetyltransferase activity (Ki = 200 microM). The NAQ exhibited noncompetitive type inhibition compared with N-methyl-3-quinuclidinol, a competitive inhibitor of HAChU. Thus, substitution at the N-functional group not only alters potency, but may change the mechanism by which inhibition is produced. The optical isomers of NAQ and several derivatives were prepared and employed to examine the stereochemical selectivity for inhibition of choline uptake. The S(+)-isomer of NAQ (IC50 = 0.1 microM) had approximately 100-fold greater inhibitory activity for HAChU than the corresponding R(-)-isomer (IC50 = 10 microM). With all other quinuclidinols tested, the S(+)-isomers were also more potent than the corresponding R(-)-isomers. In an effort to obtain a tertiary inhibitor of HAChU that would be expected to cross the blood-brain barrier following peripheral administration, 3-biphenyl-3-quinuclidinol (BHQ) and 3-naphthyl-3-quinuclidinol (NHQ) were synthesized and evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Colina/metabolismo , Parassimpatolíticos/síntese química , Quinuclidinas/síntese química , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Colina/farmacocinética , Colina O-Acetiltransferase/antagonistas & inibidores , Depressão Química , Técnicas In Vitro , Masculino , Parassimpatolíticos/farmacologia , Quinuclidinas/farmacologia , Ratos , Ratos Endogâmicos , Sódio/fisiologia , Estereoisomerismo , Relação Estrutura-Atividade , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismoRESUMO
The purpose of the study was to assess the extent and nature of malnutrition in young children in Jamaica in a manner useful for Government planning. 490 infants and young children under 4 years of age were examined in 3 urban and 7 rural localities previously studied in 1963-4. The peak period of weight failure was in children aged 9-24 months, a quarter of whom were below 80 percent of standard weight. No difference in average weights for age between 1963-4 and 1970 were detected. The peak period for height failure was between 12 and 18 months. 57 percent of the secotrants had a chest/head circumference ratio less than 1.0 and 37 percent in their fourth year were still abnormal in this respect. More children had extremely thin triceps skinfolds than had small arm muscle circumferences. The results are discussed in relation to each other and to other surveys, to mortality rates, to the food balance sheet of Jamaica and to a food consumption survey carried out in 1963-4. The conclusions are drawn that inadequate breastfeeding occurring against a back-cloth of poverty and often inadequate and inappropriate supplementation has resulted in an early onset of PCM-predominantly a deficiency of total calories rather than of protein. Malnutrition is more prevalent in rural than urban areas. No change in overall nutrition of infants and young children in Jamaica between 1963 and 1970 could be detected. (Summary)
Assuntos
Humanos , Lactente , Criança , Masculino , Feminino , Estado Nutricional , Nutrição do Lactente , Inquéritos Nutricionais , Peso Corporal , Estatura , JamaicaRESUMO
The purpose of the study was to assess the extent and nature of malnutrition in young children in Jamaica in a manner useful for government planning. 489 infants and young children under 4 years of age were examined in three urban and nine rural localities previously studied in 1963-4. The peak period of weight failure was in children aged 9-24 months, a quarter of whom were below 80 percent of standard weight. No difference in average weights for age between 1963-4 and 1970 were detected. The peak period for height failure was between 12 and 18 months. 57 percent of the secotrants had a chest/head circumference ratio less than 1.0 and 37 percent in their fourth year were still abnormal in this respect. More children had abnormally thin triceps skinfolds than had small arm muscle circumferences. The results are discussed in relation to each other and to other surveys, to mortality rates, to the food balance sheet of Jamaica and to a food consumption survey carried out in 1963-4. The conclusions are drawn that inadequate breast-feeding occurring against a background of poverty and often inadequate and inappropriate supplementation has resulted in an early onset of protein calorie malnutrition - predominantly a deficiency of total calories rather than of protein. Malnutrition is more prevalent in rural than urban areas. No change in overall nutritional status of infants and young children in Jamaica between 1963 and 1970 could be detected (AU)