title: Role of gastrin in the development of gastric mucosa, ECL cells and A-like cells in newborn and young rats.
abstract: Histamine-producing ECL cells and ghrelin-producing A-like cells are endocrine/paracrine cell populations in the acid-producing part of the rat stomach. While the A-like cells operate independently of gastrin, the ECL cells respond to gastrin with mobilization of histamine and chromogranin A (CGA)-derived peptides, such as pancreastatin. Gastrin is often assumed to be the driving force behind the postnatal development of the gastric mucosa in general and the ECL cells in particular. We tested this assumption by examining the oxyntic mucosa (with ECL cells and A-like cells) in developing rats under the influence of YF476, a cholecystokinin-2 (CCK(2)) receptor antagonist. The drug was administered by weekly subcutaneous injections starting at birth. The body weight gain was not affected. Weaning occurred at days 15-22 in both YF476-treated and age-matched control rats. Circulating gastrin was low at birth and reached adult levels 2 weeks after birth. During and after weaning (but not before), YF476 greatly raised the serum gastrin concentration (because of abolished acid feedback inhibition of gastrin release). The weight of the stomach was unaffected by YF476 during the first 2-3 weeks after birth. From 4 to 5 weeks of age, the weight and thickness of the gastric mucosa were lower in YF476-treated rats than in controls. Pancreastatin-immunoreactive cells (i.e. all endocrine cells in the stomach) and ghrelin-immunoreactive cells (A-like cells) were few at birth and increased gradually in number until 6-8 weeks of age (control rats). At first, YF476 did not affect the development of the pancreastatin-immunoreactive cells, but a few weeks after weaning, the cells were fewer in the YF476 rats. The ECL-cell parameters (oxyntic mucosal histamine and pancreastatin concentrations, the histidine decarboxylase (HDC) activity, the HDC mRNA levels and serum pancreastatin concentration) increased slowly until weaning in both YF476-treated and control rats. From then on, there was a further increase in the ECL-cell parameters in control rats but not in YF476 rats. The postnatal development of the ghrelin cells (i.e. the A-like cells) and of the A-like cell parameters (the oxyntic mucosal ghrelin concentration and the serum ghrelin concentrations) was not affected by YF476 at any point. We conclude that gastrin affects neither the oxyntic mucosa nor the endocrine cells before weaning. After weaning, CCK(2) receptor blockade is associated with a somewhat impaired development of the oxyntic mucosa and the ECL cells. While gastrin stimulation is of crucial importance for the onset of acid secretion during weaning and for the activation of ECL-cell histamine formation and secretion, the mucosal and ECL-cell growth at this stage is only partly gastrin-dependent. In contrast, the development of the A-like cells is independent of gastrin at all stages.
authors.affiliation: Department of Pharmacology, Institute of Physiological Sciences, University of Lund, Sölvegatan 19, BMC F13, S-227 34, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Björkqvist
authors.forename: Charlotta
authors.initials: C
authors.lastname: Dornonville de la Cour
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Zhao
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gagnemo-Persson
authors.forename: Rolf
authors.initials: R
authors.lastname: Håkanson
authors.forename: Per
authors.initials: P
authors.lastname: Norlén
mesh_terms: D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D053379:Chromogranin A; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D005755:Gastrins / Q000502:physiology*; D006636:Histamine Release; D008297:Male; D010187:Pancreatic Hormones / Q000032:analysis; D051381:Rats
chemical_list: D053379:Chromogranin A; D005755:Gastrins; D010187:Pancreatic Hormones; C050836:pancreastatin