SYMPOSIUM

The American Chemical Society Symposium on Agents Affecting Gastrointestinal Function

New York, New York, Sept 9, 1969

Introduction This symposium was assembled to pre-

sent several topics that are currently being emphasized in studies on the gastrointesti- nal tract. After a long period of dormancy, renewed effort in research on the gastro- intestinal tract has led to new concepts on organ function. T h e medicinal chemists should find the current informat ion of in- terest since, in part, it involves endogenous substances that have recently been purified, identified, and their function elucidated. This type of information can frequently lead to the design of chemicals that regulate or modify organ function. This introduc- tion will outline in broad terms some of the current concepts in the physiology and pharmacology of the gastrointestinal tract.

The gastrointestinal tract is a multKunc- tional organ vital to homeostasis of the organism. Absorption, secretion, and con- tractile activity are integral parts in the digestion and assimilation of ingested sub- stances. This integrative function is per- formed under the influence of an extensive interaction between the neurogenic and hormonal systems. T h e interplay is accom- plished by the tract producing and con- taining a host of various substances, some of which are biogenic amines (eg, hista- mine, serotonin, and catecholamines) ; lipid

Address for reprint requests: Dr. Paul Bass, Medical and Scientific Affairs Division, Pharma- cology Department, Parke, Davis ~ Co., Ann Arbor, Mich 48106.

soluble acids (eg, darmstoff and prosta- glandins); and polypeptides (eg, sub- stance P, secretin, gastrin, and cholecysto- kinin-pancreozymin (CCK-PZ)). Gastrin and CCK-PZ are discussed in detail by Drs. Gregory and Ondetti . T h e GI tract also contains many substances that are in need of purification and physiologic verification. Some of these are villikinin and the gas- trones--eg, urogastrone* gastrogastrone, sialogastrone, and enterogastrone. Many of these substances are currently under study for their actions on and interactions with the neurogenic elements of the gastro- intestinal tract.

T h e control of gastric acid secretion is an example of the extensive neurogenic-hor- monal interplay. Acetylcholine, the media- tor of the vagus nerve, releases gastrin from the ant rum of the stomach; acetylcholine also exerts a secretagogue effect on the parietal cells in the body of the stomach. In contrast the mediator of the sympathetic nervous system, norepinephrine, tends to reduce acid secretion.

T h e last decade has seen extensive prog- ress in the isolation, purification and syn. thesis of gastrin. T h e name "gastrin" has become a general term which can refer to the Gastrins I or II isolated from several animal species, the terminal tetrapeptide or pentapeptide. These substances, though

• See Gregory article for further detail.

Digestive Diseases, Vol. 15, No. 2 (February 1970) 139

INTRODUCTION

not equally potent , tend to exert similar biological actions. For example, because of the presence of a sulfate molecule, Gas- trin I I is a more potent s t imulant of gall- bladder contract ion than Gastrin I. Cur- rent studies indicate that gastrin has a wide spectrum of biological actions. Some of the effect~ observed with low doses of gastrin are the s t imulat ion of gastric-acid secretion, weak to modera te s t imulat ion of pancreatic secretion of H.,O and bi- carbonate, strong s t imulat ion of pancreatic enzyme secretion, and contract ion of the gastroesophageal sphincter. With high doses of gastrin, the acid secretion of the dog can actually be decreased. Gastrin can either increase or decrease smooth muscle contractions depending on tile do.~e, prepa- ration, and area of the tract. Gastrin also influences insulin release, sodium and HeO transport in the ileum, and several other biological parameters. Thus a substance that was associated initially with the con- trol of gastric secretion has been shown to have a broad spectrum of physiological and pharmacological actions.

T h e development of exogenous substances that exert an inItuence on the gastroin- testinal tract has also received renewed interest. Th i s topic has been reviewed by Butler and coworkers. Moni tor ing and evaluat ing the effects of ei ther endogenous ol exogenous substances in man are a

challenge to tile experienced clinician and require critical and objective experimental design. Tile current developnmnts in ab- sorption of drugs have been reviewed by Levine. A major effort in this area is to elucidate the relat ionship between absorp- tion of chemicals with the bidirectional movement of electrolytes and water across the mucosa. T h e area of smooth-muscle contractile activity was not discussed in this symposium. Tile development of new tech- nics with a t tent ion to the more ph,vsiologi- cal t reatment of the muscle is leading to new informat ion on motility. T h e relation- ship between contractile activity and secre- tion, absorption, or in t ra luminal transport are fertile fields for the interested investi.aa- tor.

Fur ther studies are needed on the in- fluence of endogenous and exogenous sub- stances on secretion, absorption, and con- tractile activity of the gastrointestinal tract. T h e chemists' cont inuing efforts to purify or synthesize the necessary chemical entities for study in these areas will hasten the clarification of the physiologic hmctions and biochemical reactions of the gastro- intestinal tract.

PAUL BASS, PHD Medical and Scientific Affairs Division

Pharmacology Deparlment Parke, Davis & Co.

Ann Arbor, Mich 48106

140 Digestive Diseases, VoL 15, No. 2 (February 1970)