Homeostatic control of manganese excretion in the neonatal rat

1987 ◽  
Vol 252 (5) ◽  
pp. R842-R847 ◽  
Author(s):  
N. Ballatori ◽  
E. Miles ◽  
T. W. Clarkson

Previous studies in neonatal and suckling animals showed that immature animals have a greatly diminished capacity to excrete manganese and therefore were considered to be unable to regulate tissue manganese concentrations. In contrast, the present studies indicate that suckling rats have the capacity to excrete excess manganese at rates nearly comparable to those of adults. Eight- to 10-day-old rats given a tracer dose of 54MnCl2 (essentially carrier free), either via gavage or by intraperitoneal injection showed little elimination of the 54Mn until the 18-19th day of life, when there was an abrupt increase in the rate of the metal's excretion. However, when manganese was given in doses of 1 and 10 mg/kg, the young animals excreted from 30-70% of the dose in only 4 days, at which time a new rate of excretion was achieved. This enhanced rate of excretion remained constant until the 18-19th day of life, when it was again accelerated. Biliary excretion of manganese, the primary route for the elimination of the metal, was only 30-60% lower in 14-day-old rats compared with adults at doses ranging from tracer to 10 mg 54Mn/kg. For both the 14-day-old and adult rats, an apparent biliary transport maximum was reached at a dose of 10 mg Mn/kg. These studies indicate that the excretory pathways for manganese are well developed in the neonatal rat. The avid retention of tracer quantities of manganese by the neonate may be a consequence of the scarcity of this essential trace metal in its diet.

1988 ◽  
Vol 255 (4) ◽  
pp. E525-E530 ◽  
Author(s):  
L. Witek-Janusek

The neonatal rat is very sensitive to the lethal effects of bacterial endotoxin. Because of the adaptive importance of pituitary-adrenal secretions to stress, this study examined the ontogeny of the plasma corticosterone and adrenocorticotropic hormone (ACTH) responses to endotoxin. The lethal sensitivity of young rats to endotoxin ranged from 0.5 to 30 mg/kg (ip) in the 1- to 21-day-old rat. After endotoxin treatment, the 1- and 2-day-old rat showed marked elevations of corticosterone similar in magnitude to that seen in 21-day-old and adult rats; however, significantly depressed corticosterone increments were observed in the 5-, 10-, and 14-day-old rats. This age-related pattern of adrenocortical secretion was correlated with the developing rat's corticosterone response to exogenous ACTH. In contrast, endotoxin administered to 5-, 10-, and 14-day-old rats resulted in increments of plasma ACTH similar to those observed in the 21-day-old and adult rats. Although plasma ACTH levels increased by 84-127% in the 1- and 2-day-old rats, these increases were significantly less than those of rats at all other ages tested. Thus the newborn rat mounts an effective corticosterone response to endotoxin, loses this ability between ages 5-14 days, and regains this response at 21 days of age. Because the hyporesponsive ages exhibit a marked increase in ACTH secretion, the loss of the adrenocortical response to endotoxin appears to be a result of a depressed responsiveness of the adrenal cortex to ACTH.


1978 ◽  
Vol 203 (1151) ◽  
pp. 177-189 ◽  

The transport of immunoglobulin and ferritin across the intestinal mucosa of adult rats provides an excellent model for transcellular protein transport study. Intestinal uptake and transcellular transport have been extensively studied in the neonatal rat, but not to such an extent in the adult rat. The transport of 125 I labelled bovine immunoglobulin G and ferritin was studied in 100 days old rats using intestinally administered proteins. Antigen was estimated in the tissues by reacting extracts against specific immune antiserum prepared in rats, and visualization studies were carried out by fluorescence microscopy and direct deposition autoradiography at electron microscopic level. From these studies, it can be seen that these proteins are taken up by the intestinal cells and transported, antigenically intact, across the barriers to the body organs.


1978 ◽  
Vol 234 (5) ◽  
pp. C191-C197 ◽  
Author(s):  
J. A. Hemberger ◽  
L. S. Schanker

To compare the pulmonary absorption of drugs in newborn rats (3-27 days old) with that in adults, 0.01-0.1 ml of Krebs-Ringer phosphate solution (pH 7.4) containing a drug was administered to anesthetized animals by way of a catheter introduced through a tight-fitting tracheal cannula. After various times, lungs and trachea were removed and assayed for drug that remained. Semilogarithmic plots of percent drug remaining against time yielded a straight line for each compound. The lipid-soluble drugs procaine amide and sulfisoxazole were absorbed at similar rates in newborn and adult rats. In contrast, the lipid-insoluble drugs tetraethylammonium, p-aminohippuric acid, and mannitol were absorbed approximately 2 times more rapidly in younger rats (3-12 days) than in older animals (18 day, 27 day, or adult). The results suggested that the respiratory tract membranes of 3- to 12-day-old rats have a greater porosity than those of older animals.


1977 ◽  
Vol 166 (3) ◽  
pp. 421-428 ◽  
Author(s):  
Joanne Pieringer ◽  
G. Subba Rao ◽  
Paul Mandel ◽  
Ronald A. Pieringer

The sulphogalactosylglycerolipid of rat brain is closely associated with the process of myelination, as demonstrated by the following observations. 1. The lipid is barely detectable in rat brain before 10 days of age, accumulates rapidly between age 10 and 25 days, and remains relatively constant in amount (between 0.3 and 0.4μmol per brain) thereafter into adult life. 2. The activity of adenosine 3′-phosphate 5′-sulphatophosphate–galactosyldiacylglycerol sulphotransferase is almost absent before 10 days of age, attains a maximum at age 20 days, and slowly decreases thereafter with increasing age. This developmental pattern correlates well with that of other myelin-specific metabolites. 3. Both the concentration of the sulphogalactosylglycerolipid and the activity of sulphotransferase are greatly decreased in the non-myelinating jimpy mouse. 4. The myelin fraction of rat brain contains most of the sulphogalactosylglycerolipid. The lipid occurs in a diacyl and an alkylacyl form. Determinations of the relative amount of each type in brain showed about a 1:1 mixture in both 21-day-old and adult rats. Rats injected with H235SO4 at 20 days of age lost35S from the diacyl form at a higher rate than from the alkylacyl compound over a 21-day period. These data suggest that the diacyl form has a higher turnover than the alkylacyl derivative. The percentage of the total sulpholipid content of brain contributed by the sulphogalactosylglycerolipid is 16% in 21-day-old rats and 8.4% in adult rats.


2013 ◽  
Vol 114 (4) ◽  
pp. 472-481 ◽  
Author(s):  
Heidi Kletzien ◽  
John A. Russell ◽  
Glen E. Leverson ◽  
Nadine P. Connor

Age-associated changes in tongue muscle structure and strength may contribute to dysphagia in elderly people. Tongue exercise is a current treatment option. We hypothesized that targeted tongue exercise and nontargeted exercise that activates tongue muscles as a consequence of increased respiratory drive, such as treadmill running, are associated with different patterns of tongue muscle contraction and genioglossus (GG) muscle biochemistry. Thirty-one young adult, 34 middle-aged, and 37 old Fischer 344/Brown Norway rats received either targeted tongue exercise, treadmill running, or no exercise (5 days/wk for 8 wk). Protrusive tongue muscle contractile properties and myosin heavy chain (MHC) composition in the GG were examined at the end of 8 wk across groups. Significant age effects were found for maximal twitch and tetanic tension (greatest in young adult rats), MHCIIb (highest proportion in young adult rats), MHCIIx (highest proportion in middle-aged and old rats), and MHCI (highest proportion in old rats). The targeted tongue exercise group had the greatest maximal twitch tension and the highest proportion of MHCI. The treadmill running group had the shortest half-decay time, the lowest proportion of MHCIIa, and the highest proportion of MHCIIb. Fatigue was significantly less in the young adult treadmill running group and the old targeted tongue exercise group than in other groups. Thus, tongue muscle structure and contractile properties were affected by both targeted tongue exercise and treadmill running, but in different ways. Studies geared toward optimizing dose and manner of providing targeted and generalized tongue exercise may lead to alternative tongue exercise delivery strategies.


1992 ◽  
Vol 116 (1) ◽  
pp. 167-176 ◽  
Author(s):  
D Wren ◽  
G Wolswijk ◽  
M Noble

We have been studying the differing characteristics of oligodendrocyte-type-2 astrocyte (O-2A) progenitors isolated from optic nerves of perinatal and adult rats. These two cell types display striking differences in their in vitro phenotypes. In addition, the O-2Aperinatal progenitor population appears to have a limited life-span in vivo, while O-2Aadult progenitors appear to be maintained throughout life. O-2Aperinatal progenitors seem to have largely disappeared from the optic nerve by 1 mo after birth, and are not detectable in cultures derived from optic nerves of adult rats. In contrast, O-2Aadult progenitors can first be isolated from optic nerves of 7-d-old rats and are still present in optic nerves of 1-yr-old rats. These observations raise two questions: (a) From what source do O-2Aadult progenitors originate; and (b) how is the O-2Aadult progenitor population maintained in the nerve throughout life? We now provide in vitro evidence indicating that O-2Aadult progenitors are derived directly from a subpopulation of O-2Aperinatal progenitors. We also provide evidence indicating that O-2Aadult progenitors are capable of prolonged self renewal in vitro. In addition, our data suggests that the in vitro generation of oligodendrocytes from O-2Aadult progenitors occurs primarily through asymmetric division and differentiation, in contrast with the self-extinguishing pattern of symmetric division and differentiation displayed by O-2Aperinatal progenitors in vitro. We suggest that O-2Aadult progenitors express at least some properties of stem cells and thus may be able to support the generation of both differentiated progeny cells as well as their own continued replenishment throughout adult life.


1980 ◽  
Vol 186 (2) ◽  
pp. 399-403 ◽  
Author(s):  
P G Holtzapple ◽  
C M Starr ◽  
T Morck

1. Phosphatidylcholine synthesis in the foetal, newborn and adult small intestine of rats was studied by determination of cytidine diphosphocholine-1,2-diacylglycerocholine phosphotransferase (cholinephosphotransferase) and acyl-CoA-1-acyl-sn-glycerol-3-phosphocholine acyltransferase (lysophosphatidylcholine acyltransferase) activities and the incorporation of [1-14C]oleic acid into phosphatidylcholine. 2. Cholinephosphotransferase activity was low in foetal jejunum and ileum, increased 3-4 fold in the ileum by 6 days of age and by 12 days in the jejunum. Jejunal activity remained constant throughout weaning; ileal activity gradually decreased to values 25% of that of the jejunum. 3. Lysophosphatidylcholine acyltransferase activity was high in foetal jejunum and ileum, decreased 70% immediately after birth in the jejunum and increased to adult values by 12 days of age. Ileal activity decreased by 20% after birth, but decreased more rapidly at weaning to 30% of the activity in jejunum. 4. Initial rates and steady-state incorporation of [1-14C]oleic acid into phosphatidylcholine by jejunal rings of 10 day-old rats exceeded that observed in jejunal rings from adult rats by 2-4-fold. 5. In the postnatal jejunum, neither cholinephosphotransferase and lysophosphatidylcholine acyltransferase activities nor oleic acid incorporation were stimulated by cortisone administration in vivo.


1998 ◽  
Vol 275 (4) ◽  
pp. C1143-C1150 ◽  
Author(s):  
James F. Collins ◽  
Pawel R. Kiela ◽  
Hua Xu ◽  
Jiamin Zeng ◽  
Fayez K. Ghishan

We have previously described changes in intestinal brush-border membrane vesicle (BBMV) Na+/H+exchange activity and characterized Na+/H+exchanger (NHE3) expression during rat ontogeny. The current studies were designed to investigate developmental changes in NHE2 expression in rat intestine. In previous studies, pH-dependent uptake of Na+ in jejunal BBMV utilizing HOE-694 inhibition demonstrated that NHE2 functional protein levels were lowest in 2-wk-old rats, higher in 3-wk-old and adult rats, and highest in 6-wk-old rats [Collins et al. Am. J. Physiol. 273 ( Cell Physiol. 42): C1937–C1946, 1997]. In the current investigation, Northern blot analyses showed that NHE2 mRNA levels in the jejunum were similar in 6-wk-old, adult, and 3-wk-old rats and three- to fivefold lower in 2-wk-old rats. In situ hybridization of 2- and 6-wk-old rat intestine with NHE2-specific probes confirmed Northern blot observations. Polyclonal antibodies were developed against an NHE2-specific peptide from amino acids 652–661. Western blots with NHE2 antiserum showed that the intensity of a specific 90-kDa band was lowest in 2-wk-old animals and four- to sixfold higher in 3- and 6-wk-old and adult animals. Immunohistochemical analysis showed specific staining of NHE2 antiserum to only the apical intestinal membrane. Furthermore, nuclear run-on analyses showed a 1.7-fold higher NHE2 transcription rate in 6-wk-old rats than in 2-wk-old rats. Overall, the current data suggest that increases in NHE2 expression upon weaning are mediated by increased gene transcription.


2003 ◽  
Vol 285 (6) ◽  
pp. F1100-F1107 ◽  
Author(s):  
Mohammad Asghar ◽  
Tahir Hussain ◽  
Mustafa F. Lokhandwala

Previously, we reported that natriuretic and diuretic response to dopamine is diminished in old Fischer 344 rats, which is due to higher basal protein kinase C (PKC) activity and hyperphosphorylation of Na-K-ATPase in the proximal tubules (PTs) of old rats. The present study was conducted to determine whether higher PKC activity could be due to altered expression of some of the PKC isoforms in the superficial cortex (rich in PTs) of old rats. Fluorimetric measurement showed almost twofold increase in the PKC activities in homogenates and membranes of old (24 mo) compared with adult (6 mo) rats. Interestingly, in the basal state PKC-βI was overexpressed in the membranes, whereas PKC-δ expression was increased in the cytosol of old compared with adult rats. Treatment of the cortical slices with either SKF-38393, a D1-like agonist, or PDBu, a direct activator of PKC, caused translocation of PKC-βI from cytosol to membranes in adult but not in old rats. Both of these drugs caused translocation of PKC-δ from membranes to cytosol in adult but not in old rats. These drugs had no effect on translocation of PKC-ζ in both adult and old rats. Both PKC-βI and -δ coimmunoprecipiated with α1-subunit of Na-K-ATPase in adult and old rats. These observations suggest that both SKF-38393 and PDBu differentially regulate PKC-βI and -δ in adult but not in old rats. Also, PKC-βI and -δ seem to interact with Na-K-ATPase in these animals. The overexpression of both PKC-βI and -δ in old rats could be responsible for a higher basal PKC activity, which causes the hyperphosphorylation of Na-K-ATPase and contributes to the diminished inhibition of Na-K-ATPase activity by dopamine in old rats.


2005 ◽  
Vol 289 (6) ◽  
pp. C1417-C1425 ◽  
Author(s):  
A. J. Rico ◽  
J. Prieto-Lloret ◽  
C. Gonzalez ◽  
R. Rigual

Hypoxia elicits catecholamine (CA) secretion from the adrenal medulla (AM) in perinatal animals by acting directly on chromaffin cells. However, whether innervation of the AM, which in the rat occurs in the second postnatal week, suppresses this direct hypoxic response is the subject of debate. Opioid peptides have been proposed as mediators of this suppression. To resolve these controversies, we have compared CA-secretory responses with high external concentrations of K+ ([K+]e) and hypoxia in the AM of neonatal (1- to 2-day-old) and juvenile (14- or 15- and 30-day-old) rats subjected to superfusion in vitro. In addition, we studied the effect of hypercapnic acidosis on the CA-secretory responses in the AM during postnatal development and the possible interaction between acidic and hypoxic stimuli. Responses to high [K+]e were comparable at all ages, but responses to hypoxia and hypercapnic acidosis were maximal in neonatal animals. Suppression of the hypoxic response in the rat AM was not mediated by opioids, because their agonists did not affect the hypoxic CA response. The association of hypercapnic acidosis and hypoxia, mimicking the episodes of asphyxia occurring during delivery, generates a more than additive secretory response in the neonatal rat AM. Our data confirm the loss of the direct sensitivity to hypoxia of the AM in the initial weeks of life and demonstrate a direct response of neonatal AM to hypercapnic acidosis. The synergistic effect of hypoxia and acidosis would explain the CA outburst crucial for adaptation to extrauterine life observed in naturally delivered mammals.


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