Kurt Mandrek

Effects of gastrin-releasing peptide (GRP) on the mechanical activity of the human ileocaecal region in vitro.

Mechanical activity was recorded in muscle preparations isolated from the human ileocaecal region. Gastrin‐releasing peptide (GRP, 10−9− 10−7 mol L−1) produced two types of response in the different muscle layers. Longitudinally cut strips showed a concentration‐dependent increase in the rhythmic activity, whereas the circularly orientated layers generally reacted with a small decrease in tone. These effects could not be influenced by blockade of adrenergic or cholinergic receptors or nerve blockade with tetrodotoxin (TTX). Application of pentagastrin did not mimic the action of GRP. These findings suggest a direct action of GRP on smooth muscle via distinct receptors which have already been demonstrated to exist in human gastrointestinal tract. The opposite effects on circular and longitudinal strips might indicate a modulatory role of GRP in the control of ileocolonic transit.

Action of FMRFamide-like Peptides on Porcine Gastrointestinal Motility In Vitro

Mechanical activity was recorded in circular and longitudinal smooth muscle preparations isolated from extensive regions of the porcine gastrointestinal tract in response to the FMRFamide-like neuropeptides F8Famide and A18Famide. In all preparations, the peptides were about equipotent in producing phasic contractions or enhancing spontaneous activity. The most prominent responses were observed in jejunal longitudinal strips which were on the average 91% (+/- 4% SEM, n = 15; 10(-6) M) of the histamine (10(-5) M) responses. The peptide-induced phasic activity was completely abolished by nifedipine but was unaffected by tetrodotoxin, atropine, phentolamine, yohimbine, phenoxybenzamine, propranolol, methysergide, cimetidine, indomethacin, levallorphane or naloxone. Both peptides enhanced acetylcholine-induced contractions. However, bovine ileum and guinea-pig taenia coli was not affected by these peptides. The results indicate that F8F- and A18F-amide contract porcine gastrointestinal smooth muscle by acting directly via non-opioid receptors on L-type calcium channels. In addition an increase of the sensitivity to cholinergic stimulation occurs.

Myogenic Basis of Motility in the Pyloric Region of Human and Canine Stomachs

In vitro gastric motility was investigated in 48 human and 16 canine stomachs by measuring the mechanical activity of isolated muscle strips under auxotonic conditions. For a precise regional differentiation, we recorded the mechanical activity of longitudinal and circular strips from fundus, corpus and antrum, as well as from circular preparations of the inner and outer layer of the pyloric sphincter and from the duodenum. The analysis showed that the anatomical division of the stomach into three distinct regions resulted physiologically in different patterns of contraction in vitro for each region. The fundus exhibited purely tonic spontaneous activity and a tonic contraction pattern after application of acetylcholine whereas the activity in the circular antrum was purely phasic. A combination of tonic and phasic contractions was found in the corpus and longitudinal antrum. A major difference in the basic spontaneous activity pattern was evident between man and dog. A gradient of intrinsic frequency in the stomach from proximal to distal was seen in the dog but not in man. A physiologically distinct area exists in the pyloric region of both species adjacent to the antrum and duodenum. The pyloric ring has its own spontaneous activity (minute-rhythm), reacts to the application of acetylcholine with relatively weak contractions and, unique to the dog, was delineated by histamine-induced maximal contractions. The results provide evidence that the pyloric ring is a distinct organ with specific functional characteristics in its cellular-myogenic structure.

Diameter and Wall Thickness Recording of Canine Pylorus with Implantable Miniature Ultrasonic Transducers

Outer diameter and thickness of the muscular wall of canine pylorus were measured simultaneously by determining the distance between pairs of implanted ultrasonic transducers, evaluating the sonic transit time with a digital sonometer. For the study of the motility in the gastroduodenal transit zone, the ultrasonically determined pyloric responses were compared with signals from conventional strain-gauge transducers sutured to the neighboring duodenum and gastric antrum. After stimulation of the gastrointestinal motility by an intravenous bolus injection of cholecystokinin octapeptide, pyloric contractions with a frequency of 5.2 min-1 could be recorded for some minutes; those contractions were independent of the more rapid antral and duodenal motility. Together with the observed tonic constriction of the pyloric ring, which could be inhibited by intravenous injection of adrenaline, an autonomous role of the gastroduodenal junction as a true sphincter is supported.

Contractile Action of Gastrin-Releasing Peptide on Isolated Preparations of Human Gastroduodenal Muscle

Mechanical activity was recorded in muscle preparations isolated from different regions of the human stomach (circular and longitudinal strips from fundus, corpus and antrum) and duodenum. Application of gastrin-releasing peptide (GRP, 10(-9) to 10(-7) mol/l) caused a concentration-dependent increase in the activity in all stomach strips, the height and the pattern of contraction was similar to the acetylcholine (ACh) responses (10(-7) to 10(-5) mol/l). Longitudinally cut duodenal strips were also excitable by GRP. Circularly cut duodenal strips, however, showed no responses to GRP. Both layers were excitable by ACh. The most prominent effect of GRP on longitudinal duodenal strips near the jejunum was a tonically appearing activation, which could reach up to 180% of the maximum ACh-induced activation.

Bombesin - The Most Stimulating Peptide of Human Gastric Smooth Muscle

The mechanical activity of isolated muscle strips from different regions of 33 human stomachs was measured under auxotonic conditions. After application of bombesin (stepwise increases in organ bath concentrations 10(-9) to 10(-6) mol/l) the following in vitro effects were observed in human gastric muscle: (1) Bombesin stimulated both circular and longitudinal preparations from all regions of the human stomach and circular duodenum. (2) The quality of the responses to bombesin application was dependent on the general myogenic characteristics of the preparations of the different stomach regions. The contraction pattern changed at high bombesin concentrations in the organ bath to slower fluctuations. (3) Bombesin resulted in a maximal tonic response in the pyloric region preparations. An increase in tone was usually observed in the inner pyloric preparations, being typical for the region. (4) The effects of bombesin on the human stomach were stronger than the effects of many other regulatory peptides and of the reaction to acetylcholine. (5) The bombesin-induced effects were unaltered by pretreatment with atropine or TTX. (6) The response to bombesin frequently lasted for hours after washing before reassuming the original state.

Effects of Neurotensin on Gastric Smooth Muscle of Dog and Guinea Pig

Mechanical activity was recorded in muscle preparations isolated from different regions of dog and guinea pig stomach. Neurotensin (10−11 to 10−8 mol/liter) produced three types of responses in canine gastric muscle: a small activation of tone infundic strips and in longitudinal strips from corpus and antrum; a transient inhibition of the rhythmic activity in circular strips from corpus, antrum, and outer pylorus; and a strong activation in the strips from inner pylorus. In guinea pig gastric muscle strong tonic responses were observed in circular fundic muscle strips, whereas in all other preparations the responses were negligible. All these effects were insensitive to atropine, dimethpyrindene, and tetrodotoxin. The neurotensin effect on strips from guinea pig stomach was strongly reduced in the presence of indomethacin or cortisone and markedly potentiated in the presence of arachidonic acid or prostaglandin F2α. contrast, the excitatory effect of neurotensin on canine inner pylorus was potentiated during indomethacin treatment.