Mucosal gastrin receptor. V. Development in newborn rats

Takeuchi, Ken; Peitsch, W.; Johnson, L. R.

doi:10.1152/ajpgi.1981.240.2.g163

Cited by 52 publications

(48 citation statements)

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“…has been reported to be refractory to gastrin-and its analogues due to the absence of specific gastrin receptors during the suckling period (21). From these studies, it appears quite probable that gastrin may be broken down to form a biologically active fragment which traverses the placenta and influences gastrin homeostasis in the contraplacental circulation.…”

Section: Discussionmentioning

confidence: 99%

“…In support of this possibility, we earlier reported evidence that tissue gastrin levels are abnormally elevated in the unborn fetuses of rats that had sustained an experimentally induced gastrin deficiency (13). On the other hand, there is evidence of hyposecretion of acid in several species examined during the period of neonatal hypergastrinemia (8,17,21,26), suggesting that an open negative feedback loop may also contribute to the elevation of serum gastrin levels at birth.…”

Section: Discussionmentioning

confidence: 99%

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Contraplacental Hypogastrinemic Effect of Gastrin Infusion in Sheep

et al. 1984

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SummaryInfusion of gastrin, G-171, at 0.4 pg/min into either the maternal or fetal venous circulation of six late gestation sheep was associated with increases in serum gastrin concentration in the infused circulation and reciprocal decreases in the serum gastrin concentration in the other circulation (contraplacental) that perfused the placenta. Pentagastrin infusion at 0.4 pg/min was associated with an increase in C-terminal specific gastrin immunoreactivity in both the infused and the contraplacental circulations. These observations suggest that biologically active fragments of gastrin, but not the intact molecule, may cross the ovine placenta. An alternative explanation for our results is that gastrin infusion into either the maternal or fetal circulation which perfuses the placenta may result in the release of an inhibitor (i.e., somatostatin) into the other circulation. Of broad importance, these observations indicate that although intact polypeptide hormones may not traverse the placenta, their concentrations in maternal and fetal sera may not be as independent as previously believed. Serum gastrin half-life values in late gestation sheep fetuses, lambs, and ewes were determined to be 13.7 +: 1.9, 16.7 f 2.6, and 15.2 2 2.8 min, respectively. These similar values indicate that the relatively high serum gastrin concentrations observed in near-term sheep fetuses are not the result of prolonged half-life in the fetus.Gastrin promotes growth of the gastrointestinal tract after birth (1 1, 15). Its role in the development of the fetal gastrointestinal tract, however, has not been clearly defined, nor has the regulation of fetal circulating gastrin concentration been elucidated. Gastrin appears in fetal gastrointestinal tissues and serum late in gestation, and its concentration in the serum increases rapidly, so that at birth there is hypergastrinemia relative to adults in several species (2, 4, 8, 12, 14, 17, 18, 2 1, 22, 26). In sheep, for example, fetal serum gastrin is first detected at about 117 d gestation. It increases linearly thereafter, surpassing the mean maternal serum gastrin concentration (20.0 f 1.5 fmol/ml) after 124 d gestation ( 14). By the end of gestation at 145-147 d, fetal serum gastrin concentration is approximately 3 times the maternal concentration. The lack of correlation between maternal and fetal serum concentrations of gastrin, the absence of an umbilical venoarterial concentration difference, and the demonstration of gastrin present in gastrointestinal tissue concomitant with its appearance in serum in the fetus support the hypothesis that circulating gastrin in the fetus arises from fetal tissues rather than by transplacental passage. Furthermore, as a general observation in most species, polypeptide hormones do not traverse the placenta.On the other hand, there is some evidence that maternal events influence fetal gastrin physiology. Infusion of gastrin into pregnant dogs I wk before term significantly stimulates fetal gastric secretion (5), an observation that suggests the trans...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Contraplacental Hypogastrinemic Effect of Gastrin Infusion in Sheep

et al. 1984

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“…The neonatal rat gastric mucosa is also insensitive to gastrin during the preweaning period, and this has been found to be caused by absence of the receptors for the hormone (30). In the rat, mucosal gastrin receptors appear at the normal time for weaning, even if weaning to solid chow is artificially delayed.…”

Section: Discussionmentioning

confidence: 99%

Ontogenic Studies of Gastrointestinal Function. II. Lower Esophageal Sphincter Maturation in Neonatal Beagle Puppies

1982

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SummaryThe purpose of the present study was to investigate the postnatal development of lower esophageal spincter (LES) competence in the beagle and to determine the role of gastrin in LES functional ontogeny. Eleven beagle puppies taken from two litters were studied. All puppies were allowed to suckle during the first 3 postnatal wk. In the 4th wk, all puppies were weaned, and by the 5th wk only solid chow was offered. Intraluminal manometric pressure determinations were obtained in unanesthetized, unsedated puppies using twin-lumen, 1.7 mm OD, 1 mm ID polyvinyl catheters. A 12-15 min baseline period of intraluminal pressure was monitored, after which the puppies received successive doses of 0.03, 0.1, 1.0, and 8.0 pg/kg pentagastrin (PC) SC spaced at 45-min intervals.Progressive increases in LES pressure both during basal periods and during gastric contractions and in gastric fundus (GF) pressures during gastric contractions occurred during the 1st 5 weeks of life. An increase in pressure gradient between the LES and GF during gastric contraction occurred from birth through 5 wk of age. There was no response to 0.1-8.0 pg/kg PG until postnatal days 5-6 when the LES pressure gradient in the basal state increased in response to each of these doses. There was also no significant response by the LES to PG during gastric contraction until days 11-12 when all doses of PG evoked enhancement of LES pressure.These studies suggest that an increase in LES-GF intraluminal pressure gradient develops during the initial 2 postnatal wk in this species and that this development does not involve the hormone gastrin. Later, however, the pressure gradient may depend upon both age and gastrin since a two-way analysis of variance indicated that nit only is LES pressure affected bypostnatal age and by PG dose. but that there is an interaction between ~ostnatal age and PG dose which is significant. By the fifth wk, there was an apparent dose-response effect in which the lower two doses produced increased LES pressure and the larger two doses produced decreased LES pressures. SpeculationGastroesophageal reflux (GER) in some infants may occur when the developmental interplay between endogenous gastrin concentration, increasing sensitivity to gastrin by LES, and sensitivity to gastrin by the muscular stomach proceeds abnormally. Alternatively, either the postnatal increase in LES muscle mass or the maturation of a neural pathway that mediates reflex contraction of the LES during gastric contraction, or both, may be delayed or abnormal in some children with GER. A fourth possible abnormality that may permit GER in still other infants is failure to generate the increasing gastric contraction rate and intraluminal pressures observed to occur in normal development, thus permitting delayed gastric emptying.Functional incompetence of the lower esophageal sphincter (LES) that results in gastroesophageal reflux (GER) is a common problem in infants (6,15,20,23,24,28,29). Healthy term and preterm newborn infants normally regurgitate feedings for ...

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“…Ligand binding studies have shown an increase in the number of cholinergic receptors with age in the CNS (1 1) vas deferens (12) and an increase of gastrin receptors on the parietal cell of the stomach during the newborn period (13). Functionally, the parietal cell does not produce acid in response to exogenous gastrin in the immediate newborn period in the rat, and shows increasing levels of responsiveness at the time of weaning, coincident with the emergence of gastrin receptors as detected by ligand binding studies (14,15).…”

Section: Electrical Stimulationmentioning

confidence: 99%

Developmental Differences in Neurohumoral Modulation of the Cat Lower Esophageal Sphincter

Hillemeier

Biancani

1989

Pediatr Res

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ABSTk4CT. It is possible that age-related differences in gastroesophageal function during infancy may predispose the infant to abnormalities. We have therefore evaluated developmental differences in neurohumoral modulation of lower esophageal sphincter function in the cat. These studies were performed in an in vitro setting. In the adult cat, lower esophageal sphincter smooth muscle and postganglionic inhibitory neurons are more sensitive to muscarinic agonists than in the kitten. The circular smooth muscle of the adult lower esophageal sphincter is also more responsive to neurally mediated relaxation, brought about by electrical stimulation. However, there is no difference in response to exogenous vasoactive intestinal peptide between the two age groups. These data suggest that developmental differences in neurohumoral modulation of the lower esophageal sphincter occur in the cat. Studies of receptor activity in the LES during the newborn period would be of interest as GER is common during this period and decreases in frequency towards the end of the first year of life. Little attention, however, has been paid to modulation of LES activity during the newborn period. In vitro studies in the opossum ( 5 ) and in vivo studies in the beagle pup (6) suggest that the infant LES responds less than the adult to exogenous gastrin.The possibility that developmental differences in modulation of LES function may predispose the newborn LES to incompetence leads to the present investigation in which we propose to examine the development of neurohumoral modulation of LES pressure. Abbreviations MATERIALS AND METHODSGER, gastroesophageal reflux LES, lower esophageal sphincter TTX, tetrodotoxin VIP, vasoactive intestinal peptide DMPP, 1,l-Dimethyl-4-phenylpiperazinium iodidine GER is a common occurrence during infancy, resulting in significant morbidity (1). Although it is reasonable to expect that abnormalities in LES function may be the cause of infant GER, the developmental differences responsible for this phenomenon are unclear.The newborn infant undergoes many physiologic adaptations during development. We have recently shown that the kitten LES is unable to produce intraluminal pressure as high as the adult (2) despite being able to generate high amounts of stress in the LES circular muscle layer. This apparent contradiction is explained by the finding that the kitten LES has reduced thickness and thickness/radius ratio in the circular muscle layer, which causes a mechanical disadvantage in generating in vivo LES pressure.Cat LES tone, in vitro, is myogenic as it is not affected by TTX although LES relaxation is neurally mediated. In vivo LES C.H. is a recipient of NIH Grant 5R29-HD20054-02 and P.B. is a recipient of NIH Grant DK-RO 28614.Our study was performed on 6-wk-old recently weaned kittens and adult cats 3-5 kg in wt. After midline laparotomy, the LES was identified, and a suture was placed on the outer surface of the esophagus at the location of the high pressure zone as described previously (7).Stomach, LES, and...

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Mucosal gastrin receptor. V. Development in newborn rats

Cited by 52 publications

References 0 publications

Contraplacental Hypogastrinemic Effect of Gastrin Infusion in Sheep

Contraplacental Hypogastrinemic Effect of Gastrin Infusion in Sheep

Ontogenic Studies of Gastrointestinal Function. II. Lower Esophageal Sphincter Maturation in Neonatal Beagle Puppies

Developmental Differences in Neurohumoral Modulation of the Cat Lower Esophageal Sphincter

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