Nutrition, Digestion, Metabolism

Proceedings of the 28th International Congress of Physiological Sciences, Budapest, 1980

T. Gáti, L. G. Szollár, Gy. Ungváry

• Publisher: Pergamon
• Year: 2013
• ISBN:
  9781483189970
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

Advances in Physiological Sciences, Volume 12: Nutrition, Digestion, Metabolism covers the proceedings of the 28th International Congress of Physiological Sciences, held in Budapest in 1980, which mainly focuses on human nutrition, digestion, and metabolism. This compilation is divided into eight parts. This text first gives an introduction to vitamins and trace elements, including its role, effects, and influences on human biological processes. This book then explains the role of cyclic nucleotides in stimulus—secretion coupling of exocrine glands and the physiological components of the gastric mucosal barrier, along with their role in mucosal defense. Motility in control of gastric emptying; intestinal polypeptides and peptidergic nerves; and molecular changes during metabolic processes of gastrointestinal peptide hormones are also tackled. This text also introduces the factors involved in the integrated mechanism of intestinal absorption. This book concludes by explaining the lipoprotein metabolism, apolipoproteins, and lipid constituents. This publication will be invaluable to those in the field of physiological sciences interested specifically in studying human nutrition, digestion, and metabolism.

HORMONAL RECEPTORS IN THE CELL REGULATION OF DIGESTIVE FUNCTIONS

Serge Bonfils, Unité de Recherches de Gastroentérologie, INSERM U. 10, Hôpital Bichat, F-75877 PARIS CEDEX 18, France

Publisher Summary

This chapter describes hormonal receptors in the cell regulation of digestive functions. The main digestive functions can be activated or inhibited by hormones secreted by the GEP system. Strong evidence has been presented for action of these hormones on: (1) exocrine secretions, (2) motor activities (tonic and propulsive), and (3) function of survival, that is, tissue metabolism and cell renewal. The contribution of receptor studies to the knowledge of digestive physiology is impressive. This can be exemplified in the field of general concepts. The ability to compete for the same receptor makes it possible to explain the common behavior of structurally related hormones (gastrin family, secretin family). The knowledge of receptor structural requirements is a crucial clue in the synthesis of competitive inhibitor such as modified gastrin. Pharmacological and physiological interactions of hormones are better understood taking into account receptor events such as cooperativity and spareness phenomena. Speculation on abnormal digestive functions in pathological conditions could be more fruitful in hypothesizing possible change in the number or the sensitivity of the receptors.

The main digestive functions can be activated or inhibited by hormones secreted by the GEP system. Strong evidence has been presented for action of these hormones on: 1) exocrine secretions (water and electrolytes, proteins and glycoproteins); 2) motor activities (tonic and propulsive), 3) function of “survival”, i.e. tissue metabolism and cell renewal. Less documented and still controversial are the possible effects on other endocrine secretions and on absorption, mainly by transcellular pathway.

But as indicated in table I, there is so far no strict identities between tissues undergoing hormonal influences and tissues (or cells) evidencing receptor activation and/or inhibition by the same hormones.

HORMONAL DEPENDENCE OF DIGESTIVE FUNCTIONS

Comparison between evidences for hormonal receptor and for physiological actions at the organ level (-: no evidence so far; ?: no direct evidence).

The concept of hormonal receptor is however highly stimulating; it particularly implies the cellular events resulting from hormone-tissue interactions, that could be considered as representative of function(s) (3). This could lead to controversial results when compared with organ physiology, all the more that in experimental approaches concerned with these effects, problems arise from the multiplicity of the GEP hormones that may interfere on a same target organ and the capability for one hormone of triggering simultaneously various physiological activities. A prerequisit for optimizing reliability and reproducibility of studies appears thus to minimize or suppress the other parameters of regulation, i.e. nervous influx, feed-back phenomena driven by the digestive secretions, blood supply.

I FUNCTIONAL MODELS AT THE CELL LEVELS

Ideally, receptor studies should not only encompass binding parameters, but extend to specific functional activities: technically the methods used taken alone, are well defined and rather sophisticated; however, for an ideal demonstration, four criteria should be fulfilled. 1) Homogeneity of the tissue, i.e. constituted of one cell type (eventually equipped with more than one receptor type). 2) Specificity of hormone binding to receptor; this technically needs radiolabed hormones with full biological activities. 3) Characterization and measurement of intracellular messenger activities, in connection with 2 and 4. 4) Determination of the most relevant activity of the cell for assessing the functional response. These criteria which cover the succession of events intervening in the cell regulation of digestive functions are not often simultaneously obtained (table II).

Table II

CRITERIA FOR RECEPTOR STUDIES

CRITERIA	REQUIREMENTS
1. Homogeneity of the tissue	Isolated cells Enrichment in one cell type Group of cells with a predominant functional activity
2. Specificity of the binding	Radiolabeled hormones with full biological activity Distinction of various types of sites
3. Intracellular messenger activities	cAMP, cGMP, Ca^++, protein kinases
4. Functional responses	Specific and/or relevant for organ physiology
5. Competence within the E.Ds.	obtained from 2., 3., 4.

Isolated Cell Models

They are largely used as intact and living cells derived from various tissues: stomach fundic mucosa with isolation and separation of parietal and non-parietal cells (8, 13); pancreas acinar cells (3); enterocytes (5). Two of the four above criteria may be parallely obtained, i.e. homogeneity of the tissue and specificity of hormone binding; this specificity, not only derives from the tissue homogeneity but also from the presence of the hormone in its native condition, at a precisely known concentration and without interferences of blood supply and/or nervous influx.

On the other hand, assessing relevant activity(ies) of the cell is often difficult due to the decrease and/or to the change in cell activity when separated from normal tissue structures. Furthermore, often the biological signal is not easily characterized in the survival medium where the cells are tested: for instance acid secretion of the parietal cells can be only indirectly evidenced with the trapping of the C labelled weak basis aminopyrine. Pancreatic acinar cell activity is easier to assess by measuring amylase output. O₂ consumption (12) is a usefull tool when the specific functions of the cells have close relation with oxydative metabolism. On the whole, the sensitivity of these models is poor (table III).

Table III

ISOLATED CELL MODELS

ADVANTAGES	DISADVANTAGES
Receptors: direct access	Loss of cell polarisation
Stimulant: not metabolised local concentration precisely known	Weak Marginal Abnormal Biol. response
No interference from: blood supply nervous influx	Inadequacy to organ physiolog

Membrane models, such as vesicles, cannot be studied by reference to a specific biological response. Measurement of intracellular messenger activities is usually considered as representative of the biological response, but cannot ascertain the physiological interest of the results. Even if some kinds of biological activity are characterized (e.g. change in intravesicular pH or ion transports), their relevance to physiology may remain disputable.

From tissue or cells one can obtain rough homogenates and further purifications increase the specificity of binding and/or messenger studies. However, the homogeneity of the original material remains the most determinant factor for specific hormone receptor studies.

Isolated cells models have evidenced a number of cell-hormone relationships that could be interpreted in respect to receptor:

- affinity of one hormone for one cell type, considering the presence of one or multiple receptor type(s) (e.g. high and low affinity);

- variety of hormone receptors for one cell type; site to site interactions;

- determination of the number of sites per cell;

- ability for one receptor-type to recognize various molecular forms of one hormone or various hormones;

- internalization of receptors suggesting intracellular hormone transport.

Isolated cell models have been particularly fruitful in the following studies:

- parietal cell receptors (7): binding and stimula...

Table of contents

• Cover image
• Title page
• Table of Contents
• ADVANCES IN PHYSIOLOGICAL SCIENCES
• Copyright
• FOREWORD
• PREFACE
• Chapter 1: HORMONAL RECEPTORS IN THE CELL REGULATION OF DIGESTIVE FUNCTIONS
• Chapter 2: REVISED CONCEPT OF FUNCTIONAL AND STRUCTURAL ORGANIZATION OF THE ENZYME-TRANSPORT SYSTEMS OF THE APICAL MEMBRANE OF THE ENTEROCYTES
• Vitamins and trace elements
• Role of cyclic nucleotides in stimulus–secretion coupling of exocrine glands
• Physiological components of the gastric mucosal barrier and their role in mucosal defense
• Motility in control of gastric emptying
• Intestinal polypeptides and peptidergic nerves
• Molecular changes during metabolic processes of gastrointestinal peptide hormones
• Factors involved in the integrated mechanism of intestinal absorption
• Lipoprotein metabolism, apolipoproteins, lipid constituents
• INDEX