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Biomedical subjects

L Demling

Publications and source records attributed to L Demling.

At least 181 records · Page 10Linked to original sources
PubMed1976

Effect of 13-Nle-motilin on small intestinal transit time in healthy subjects.

In 6 female subjects without gastrointestinal diseases, 13-norleucine motilin (13-Nle-M) synthetic and biological analogue of the duodenal polypeptide, motilin, caused acceleration of intestinal transit time. Intravenous infusion of 0.4 mug/kg-h of 13-Nle-M reduced mean transit time by 50 percent. No side effects occurred during infusion of the polypeptide. Radiographic appearance of small intestinal peristalsis and mucosal relief was not influenced by 13-Nle-M.

Female↗
PubMed1976

Relationship of plasma motilin response to lower esophageal sphincter pressure in man.

The effect of intraduodenal instillation of 0.1 N hydrochloric acid or 0.9% saline (control) on lower esophageal sphincter pressure (LESP) and plasma motilin concentrations was studied in five normal volunteers. After acid, LESP and plasma motilin rose concomitantly exceeding basal by about 80% (p less than 0.025) and 90% (p less than 0.05), respectively, at 3 to 4 minutes. Control values did not significantly differ throughout the test period from the mean basal level. These results are compatible with the view that the increase in LESP after duodenal acidification may be mediated by endogenously released motilin.

Adult↗
PubMed1976

Gastroduodenal motor response to natural motilin and synthetic position 13-substituted motilin analogues: a comparative in vitro study.

Motor effects of graded concentrations of pure natural porcine motilin (13-Met-M) and synthetic motilin analogues - the methionine in position 13 substituted with either norleucine (13-Nle-M) or leucine (13-Leu-M) - on the rabbit, guinea-pig, rat, and human gastrointestinal smooth muscle were examined in vitro. Congruent species specificity of the motor activity of the motilins under study could be demonstrated in that muscle strips from rabbit and man were highly sensitive, whereas guinea-pig and rat preparations proved refractory to the polypeptides. In rabbit duodenal muscle and fundic muscle of the human stomach, graded concentrations of 13-Met-M, 13-Nle-M, and 13-Leu-M, respectively, produced graded increases in the contractile responses. The concentration-response curves were superimposable. Calculated maximal contractile responses (CMR's) and polypeptide doses for one-half maximal responses (D50 values) were not significantly different between the three motilins. Moreover, pharmacological analysis revealed that the motor effects of 13-Met-M, 13-Nle-M, and 13-Leu-M are uniformly not mediated via nervous pathways: neither blockage of axonal conduction by tetrodotoxin nor anticholinergic action by atropine exerted any detectable influence. Viewing the data presented, one may conclude that in man and rabbit, 1) natural porcine motilin and its synthetic position 13-substituted analogues, 13-Nle-M and 13-Leu-M, are of equal efficacy for gastroduodenal motor activity, and 2) position 13 of the amino acid sequence of motilin (22-residue chain) is not pertinent to the active site of the molecule.

Acetylcholine↗
PubMed1976

Effects of 13-nle-motilin on the electrical and mechanical activity of the isolated perfused canine stomach and duodenum.

Synthetic 13-norleucine-motilin (13-nle-motilin), structural and biological analogue of the naturally-occurring duodenal polypeptide, motilin, is known to stimulate antral and duodenal motor activity in vitro, but delays gastric emptying in man. In this study the direct actions of the synthetic polypeptide on myoelectrical activity and intraluminal pressure have been studied in the isolated vascular-perfused canine stomach and duodenum. 13-nle-motilin increased intraluminal pressure in the pylorus and duodenum, and dose-response analysis showed the duodenum to be twice as sensitive as the pylorus to the polypeptide. Pressure changes in the antrum were small and not dose-related, but, whereas the basic electrical rhythm in the duodenum was not altered, slow wave frequency, rhythm, and propagation in the antrum were disturbed. Electronic analysis of the duodenal spike increase which accompanied pressure rises demonstrated correlations between increases in spikes, intraluminal pressure, and dose. These results show that the direct effect of the polypeptide on adjacent organs may explain the combination of increased motor activity with delayed gastric emptying as a consequence of disturbance in the co-ordination between antrum, pylorus, and duodenum.

Animals↗
PubMed1976

Gastric mucosal blood flow and pepsin secretion in dogs--stimulation by 13-nle-motilin.

In response to graded doses of intravenous 13-norleucine-motilin (13-nle-motilin)--a synthetic analogue of motilin and biologically equivalent to the natural polypeptide-, gastric mucosal blood flow (GMBF) in canine vagally denervated fundic pouches was studied using the aminopyrine clearance technique. As 13-nle-motilin did not exert any detectable effect on gastric secretion of hydrogen ions, intraluminal instillation of 160 mM HCl was used to provide a pH gradient allowing aminopyrine to move into the pouch lumen. With increasing doses of 13-nle-motilin, GMBF increased to 148% of control values; pepsin secretion - due to augmented pepsin concentration - rose concomitantly. Enhanced pepsin secretion was not accompanied by an increase in cyclic 3',5'-adenosine monophosphate secretion.

Aminopyrine↗
PubMed1976

Bicarbonate and cyclic AMP content of pure human pancreatic juice in response to graded doses of synthetic secretin.

In seven healthy volunteers pure pancreatic juice was obtained by endoscopic cannulation of the papilla of Vater. Synthetic secretin was intravenously infused in doses doubled every 20 min. The volume of pancreatic juice was proportional to the log of the secretin dose. A significant rise (P less than 0.05) in pancreatic juice flow was elicited at a dose as low as 8.05 ng per kg per hr. Maximum flow rate approximating 250 mul per 5 min per kg of body weight was attained during infusion of 129 ng per kg per hr. At the same dose maximal bicarbonate outputs averaging 383 muEq per hr per kg of body weight were obtained, whereas bicarbonate ion concentration approached peak values (135 +/- 9 muEq per ml) at 32.2 ng per kg per hr. Bicarbonate concentrations showed a tendency to fall at supramaximal doses. The effect of increasing secretin doses on bicarbonate and cyclic AMP concentrations was remarkably similar (rs = 0.635, P less than 0.001) suggesting the participation of cyclic AMP in human pancreatic bicarbonate secretion.

Adult↗
PubMed1976

Cyclic AMP and bicarbonate responses of the dog pancreas to vasoactive intestinal peptide (VIP) and secretion.

The effects of secretin (3 CU per kilogram) and vasoactive intestinal peptide (VIP; 8 mug per kilogram) on bicarbonate and cyclic AMP secretions in pancreatic juice (with pancreatic duct perfusion) and on pancreatic tissue cyclic AMP were investigated as a function of time in 13 anesthetized dogs. The peptides were given by rapid intravenous injection. Even 30 sec. after peptide administration, tissue cyclic AMP levels were elevated, reaching peak values within the first minute and a second peak at about 3 min. Bicarbonate and cyclic AMP secretions in pancreatic juice started with a lag of 1 min. after peptide injection. Following the injection of VIP, peak pancreatic response developed within the first 5 min. and the pancreatic response actually disappeared after 15 min., whereas secretion evoked by secretin was sustained for at least 30 min. The mean +/- S.D. observed maximal bicarbonate response to VIP (100 +/- 49 muEq./5 min.) was about one sixth of the maximum output following secretin (592 +/- 181 muEq./5 min.). Increases in pancreatic tissue and juice cyclic AMP caused by VIP were significant (p less than 0.05) at 1 and 4 min.; however, they were but moderate if compared with the rise achieved by secretin. The results presented confirm previous reports that VIP is a secretin-like partial agonist of pancreatic bicarbonate secretion and are compatible with the hypothesis that both secretin and VIP elicit canine pancreatic bicarbonate secretion via the second messenger system of cyclic AMP.

Animals↗
PubMed1976

Motilin and motilin analogues: mode of action.

Natural porcine motilin (13-methionine-motilin) and its synthetic position 13-substituted analogues, 13-norleucine-motilin and 13-leucine-motilin, are of equal efficacy for gastrointestinal motor activity. Pharmacological in vitro analysis reveals that motilin effects on the gastrointestinal muscle are not mediated via nervous pathways but are brought about by direct action of the polypeptide on the muscle cell. As the contractile response to motilin can be abolished by the Ca++ antagonistic compound verapamil, a role for motilin in the transport of Ca++ to the cytosol of intestinal smooth muscle might be considered. Ca++ fluxes seem to be linked to intracellular cyclic guanosine-3':5'-monophosphate and the antagonistic cyclic adenosine-3':5'-monophosphate. By contrast, in motilin-stimulated gastric pepsin secretion, there is no evidence for a mediating role of cyclic nucleotides. It is more likely that the pepsigogic effect is brought about by augmented gastric mucosal blood flow.

Animals↗
PubMed1976

Effect of 13-Nle-motilin in postoperative ileus patients: a double-blind trial.

In this study, the effect of 13-norleucine motilin (13-Nle-M) on post-cholecystectomy ileus was assessed in 6 female patients. 13-Nle-M given by continuous i.v. infusion (0.4 mug/kg-h) on the second and third day following surgery did not influence the manifestation and duration of intestinal paralysis in comparison to 6 control patients treated with 0.9% saline. Bowel sounds, however, were more pronounced in the 13-Nle-M-group. Blood pressure and pulse rate were not influenced by the polypeptide, and no other side effects were seen, either.

Adult↗
PubMed1976

Interaction of somatostatin and pentagastrin on lower oesophageal sphincter pressure (LESP) in man.

The effect of intravenous somatostatin on basal and gastrin-stimulated human lower esophageal sphincter pressure (LESP) was examined with the rapid pull-through technique. In a group of 7 healthy volunteers LESP was not influenced under basal conditions, but there was an augmented response to pulse-doses of pentagastrin (0.6 mug/kg) during infusion of somatostatin (250 mug/kg-h). The physiological importance of these findings still has to be evaluated.

Drug Synergism↗
PubMed1976

Lack of gastric effects of S-(carboxy-methyl)-L-cysteine.

In 10 male subjects, the effects of oral S-(carboxy-methyl)-L-cysteine (SCMC) -- a mucolytic agent useful in the treatment of chronic obstructive bronchitis -- on gastric secretion of acid and N-acetylneuraminic acid (NANA) containing glycoproteins were investigated. Gastric acid outputs and mucus secretory rates remained unchanged during a 10-day period of daily administration of SCMC. Thus, the receptors of SCMC in the bronchial system appear to differ basically from those in the stomach.

Carbocysteine↗