Biomedical subjects

S E Lappi

Publications and source records attributed to S E Lappi.

24 records · Page 2Linked to original sources

PubMed1989

Effects of prenatal terbutaline exposure on cellular development in lung and liver of neonatal rat: ornithine decarboxylase activity and macromolecules.

Endogenous beta-adrenergic input has been hypothesized to control patterns of cellular maturation in sympathetic target tissues by providing a timing signal for patterns of cell replication, differentiation, and responsiveness. In the current study, we examined the consequences of fetal exposure to a beta-agonist, terbutaline (2 or 10 mg/kg on gestational d 17, 18, and 19), in developing rat lung and liver, as assessed with ornithine decarboxylase activity and measurements of tissue macromolecules. Drug treatment caused an acute stimulation of ornithine decarboxylase in fetal and neonatal lung and blunted the peak of enzyme activity seen at 20-30 d postnatally without affecting acute responsiveness to beta-adrenergic stimulation (isoproterenol). Consistent with these results, patterns of cell replication and differentiation were altered, characterized by a deficit in cell acquisition (DNA content); in the tissue displaying fetal ODC stimulation (lung), there was also evidence for developmental abnormalities in RNA and protein. Thus, by prematurely stimulating beta-adrenergic receptors, prenatal administration of adrenergic agonists may have long-lasting, adverse effects on tissue development and responsiveness.

Animals↗

PubMed1989

Selective linkage of beta-adrenergic receptors to functional responses in developing rat lung and liver: phosphatidic acid phosphatase, ornithine decarboxylase and lung liquid reabsorption.

Neurotransmitter receptors may exhibit transient linkage to specific developmental processes involved in physiological adaptation to extrauterine life and in cell maturation. We have examined the responsiveness of the developing rat lung to beta-adrenergic agonists, using fluid reabsorption, phosphatidic acid phosphatase (an enzyme involved in surfactant synthesis) and ornithine decarboxylase (an enzyme related to cellular development) as markers of these activities. The ability of beta-adrenergic agonists to stimulate phosphatidic acid phosphatase and to cause liquid reabsorption first appeared just before birth, a period in which few receptor binding sites are present; the reactivity of both these processes declined after birth, but the enzymatic stimulation reached a second peak of response during the second and third postnatal weeks. The ability of beta-adrenergic challenge to elicit stimulation of lung phosphatidic acid phosphatase then declined into adulthood, despite the fact that receptor binding sites are increasing during the same period. Lung ornithine decarboxylase activity was poorly linked to beta-receptors in the immediate perinatal period and reached a peak of reactivity during the late postnatal period in which the coupling to phosphatidic acid phosphatase was lost. The pattern for phosphatidic acid phosphatase and liquid content was selective for the lung, as no stimulatory effects were seen for these variables in the liver, despite the comparable beta-adrenergic effects on ornithine decarboxylase in the two tissues. These data suggest that, during development, the coupling of receptors to specific cellular events is more important than the number of receptor sites in determining the pattern of physiological and cellular responses mediated by neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

PubMed1989

Effects of prenatal nicotine exposure on development of central and peripheral cholinergic neurotransmitter systems. Evidence for cholinergic trophic influences in developing brain.

The development of cholinergic systems in brain regions was evaluated biochemically in developing control rats and rats whose mothers received nicotine via continuous minipump infusion during gestational days 4 to 20. The cerebral cortex displayed a unique maturational pattern of choline acetyltransferase (ChAT) activity and high-affinity synaptosomal [3H]choline uptake capabilities, characterized by increases in the concentration of these components and a postnatal spike of neuronal activity as assessed with the uptake/ChAT ratio; the peak of activity coincided with the time at which neurogenesis declines and synaptogenesis rises. Evaluation of the same markers in midbrain + brainstem indicated rises in uptake which were relatively unselective, primarily reflecting tissue growth and no postnatal peak of uptake/ChAT; cerebellum likewise showed primarily tissue growth-related changes in ChAT rather than increases in its specific concentration. Prenatal exposure to nicotine had a marked adverse effect on developmental patterns of ChAT, uptake and uptake/ChAT only in cerebral cortex, the region previously shown to exhibit major abnormalities caused by this drug and other treatments with cholinomimetic effects. ChAT was unaffected in peripheral projections to the adrenal. Nicotine may thus selectively disrupt central nervous system development by stimulating nicotinic receptors which are present in fetal brain, prematurely eliciting the events ordinarily triggered postnatally by cholinergic projections.

Animals↗

PubMed1989

Neonatal sympathectomy compromises development of responses of ornithine decarboxylase to hormonal stimulation in peripheral tissues.

The onset of sympathetic innervation has been shown to play a role in the development of postsynaptic reactivity to stimulation. In the current study, we examined whether this relationship extends to responses evoked by hormonal stimuli. Rats denervated at birth by 6-hydroxydopamine treatment showed an impaired ability of vasopressin or angiotensin to stimulate cardiac ornithine decarboxylase activity. In the kidney, responsiveness was affected only for vasopressin and in the lung denervation had only transient effects on the hormonal responses. These results confirm that sympathetic input is required for proper development of some, but not all hormonal responses; the tissue specificity suggests a role of neural factors selective for cardiac development.

Angiotensin II↗

PubMedDate not supplied

Prenatal terbutaline exposure in the rat: selective effects on development of noradrenergic projections to cerebellum.

Terbutaline, used in the treatment of premature labor and asthma, crosses the placenta and can stimulate beta 2-adrenergic receptors in the fetus. This study examines the effects of prenatal exposure to terbutaline (10 mg/kg SC on gestational days 17, 18 and 19) on the development of noradrenergic projections in brain regions of the fetal and neonatal rat, using synaptosomal uptake of [3H]norepinephrine as a marker for synaptogenesis. Although terbutaline exposure did not compromise body or brain region growth, uptake was adversely affected selectively in the cerebellum, a region which also displays close coupling of fetal beta 2-receptors to control of cell development near term. These results thus provide biochemical evidence that terbutaline may be a neurobehavioral teratogen.

Animals↗

PubMedDate not supplied

Deficits in development of central cholinergic pathways caused by fetal nicotine exposure: differential effects on choline acetyltransferase activity and [3H]hemicholinium-3 binding.

Nicotine has been hypothesized to induce neurobehavioral teratology by mimicking prematurely the natural developmental signals ordinarily communicated by the ontogeny of cholinergic synaptic transmission. In the current study, the effects of fetal nicotine exposure (2 mg/kg/day or 6 mg/kg/day) on development of central cholinergic pathways were examined in striatum and hippocampus of animals exposed from gestational days 4 through 20, using maternal infusions with osmotic minipumps. Brain region weights and choline acetyltransferase activity, an enzymatic marker for development of cholinergic nerve terminals, were within normal limits in the nicotine-exposed animals. However, development of [3H]hemicholinium-3 binding which labels the presynaptic high affinity cholinergic transporter, was deficient in both striatum and hippocampus. Abnormalities occurred during two distinct phases; in the early neonatal period, when [3H]hemicholinium-3 binding sites are transiently overexpressed, and during or after the period of rapid synaptogenesis, when binding in controls is rising consequent to the increase in nerve impulse activity. These data thus indicate that fetal nicotine exposure, even at doses that do not cause overt signs of maternal/fetal/neonatal toxicity or growth impairment, influences both specific gene expression of cholinergic nerve terminal markers, as well as indices of neuronal function. Comparison of regional selectivity at the two dose levels indicated greater sensitivity of the striatum, a region with a prenatal peak of neuronal mitosis, as compared to hippocampus, where mitosis peaks postnatally; the regional differences are consistent with vulnerability to nicotine during a critical phase of cell development.

Acetylcholine↗