Nervous control of gastrointestinal motility is extremely complex, is regulated by the enteric system, the "brain of the gut", and modulated by extrinsic nerves. This system with its multiplicity of transmitters and receptors does not always allow a clear interpretation of experimental data, especially with compounds lacking specificity. In this review the complex situation is described particularly in relation to receptor populations (cholinergic, adrenergic, dopamine, histamine, 5-hydroxytryptamine, opioid, gamma-aminobutyric acid (GABA), prostanoid and dihydropyridine receptors), therapeutic aspects of drugs and their usefulness in children. Newer principles with known drugs and promising new compounds with a more appropriate kinetic or fewer side-effects, deriving from distinct pharmacological groups, as candidates for the treatment of gastrointestinal disorders are considered e.g. anticholinergics (prifinium or actilonium bromide), adrenergic alpha 2-agonists (clonidine, lidamidine) for diarrhoea in diabetic neuropathy, adrenergic beta-blockers for shortening postoperative ileus (propranolol), dopamine receptor antagonists (metoclopramide, domperidone, alizapride) and another prokinetic substance (cisapride) which may be useful for a number of applications as gastro-oesophageal reflux, gastro-paresis, intestinal pseudo-obstruction, cystic fibrosis and constipation, morphine derivatives (e.g. loperamide) for intractable diarrhoea and calcium antagonists (e.g. nifedipine) for achalasia. Increasing experience in digestive tract pharmacology and reliable clinical studies will furthermore be the basis for a more specific and better tolerated therapy of gastrointestinal motility disorders in adults and children.

SUMMARYThe existence of a delayed inhibition of the secretion of protein by the rat pancreas after intraduodenal injection of oleic acid has been confirmed.1. This phenomenon is not dependent on the presence or absence of bile or pancreatic juice in the intestine.2. The action of oleic acid is not a pathological-phenomenon due to lesions of the gut mucosa because isotonic solutions of Na oleate dispersed into polysorbate 80 or olive oil (rich in oleic acid) plus pancreatic juice have the same effect.3. Fatty acids must be free or saponified but not esterified in the form of triglycerides. Triglycerides are only effective if pancreatic juice is simultaneously reintroduced into the duodenum.4. Oleic acid (C18 monoene) is more efficient than caprylic acid (C8) and butyric acid (04) is ineffective. The effect of chain length in releasing the inhibitory factor is therefore approximately the same as in CCK-PZ release.5. Intraduodenal infusion of hypertonic glucose solution does not inhibit pancreatic protein secretion indicating that release of enteroglucagon is probably not responsible for the inhibition. The inhibitory action of hypertonic NaCl solution is not explained.

The review describes gastrointestinal receptors which are of therapeutic interest for the treatment of motility disorders. It updates the present knowledge on muscarinic, adrenergic, dopamine, opioid and dihydropyridine receptors, their subtypes, cellular sites and functional role as drug targets. On the basis of this pharmacological receptor concept, drugs like bethanechol, clonidine, lidamidine, metoclopramide, domperidone, cisapride, loperamide and nifedipine are evaluated in proven and potential indications. In view of the very complex regulation of motility, our understanding of receptors is still fragmentary and our tools to treat motility disorders do not fulfil all therapeutic requirements. This review tries to point out the areas of particular need for further basic research and the prospects of further drug development.

T-lymphocyte subsets and human T-cell lymphotropic virus type III antibody prevalence were studied in African patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), and in female prostitutes. African blood donors and healthy Zairian and Rwandese persons matched for age, sex, and annual income served as controls. Seropositivity was noted in 46 (87%) of 53 patients with AIDS, 29 (88%) of 33 patients with ARC, 67 (80%) of 84 prostitutes, and five (12.5%) of 40 and eight (15.5%) of 51 healthy controls and blood donors, respectively. Patients with AIDS and ARC had a significantly lower OKT4/OKT8 ratio than healthy African controls. These studies suggest that human T-cell lymphotropic virus type III infection has already spread extensively into the general African population and that female prostitutes could be an important human reservoir of AIDS virus in the heterosexual population.

Exocrine pancreatic secretion is under partial control of endocrine pancreatic hormones. We studied the interaction of three doses of acetylcholine (Ach), a stimulator of exocrine and endocrine pancreatic secretion, with one dose of gastric inhibitory polypeptide (GIP) which is strongly insulinotropic, but has no effect on exocrine pancreatic secretion. The effects of Ach and GIP on insulin secretion from the rat pancreas were additive at 0.05 × 10^-6M Ach and slightly, but not significantly less than additive at 0.25 or 2.5 × 10^-6M Ach. GIP had an augmenting effect on amylase and volume secretion from the pancreas, when pancreatic secretion was stimulated by 2.5 × 10^-6M Ach, but not by 0.05 or 0.25 × 10^-6M. Exogenous rat insulin could exert an effect similar to that of GIP, although a higher dose was required. Atropine inhibited the effect of Ach on exocrine and endocrine pancreatic secretion, but not the insulinotropic action of GIP. It is hypothesized that GIP could play a role in regulating exocrine pancreatic secretion by its insulinotropic action.