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Biomedical subjects

H D Allescher

Publications and source records attributed to H D Allescher.

At least 109 records · Page 6Linked to original sources
PubMed1993

Differential effects of selective neurokinin agonists on phasic and tonic activity in rat ileal longitudinal muscle.

To test the hypothesis that different neurokinin receptors might be involved in the generation of either phasic or tonic muscular activity, selective ligands for the 6 neurokinin-1-receptor, [Sar9, Met(O2)]-SP, the neurokinin-2-receptor, [Nle10]-NKA4-10, and the neurokinin-3 receptor, [beta Asp4,MePhe7]-NKB4-10, were used to evaluate the excitatory effects of these agonists in the longitudinal rat ileal muscle in vitro. The excitatory effect was analyzed as total response (area under the curve) and as tonic or phasic (area under or within the peaks) activity. Substance P (SP, relative amount of phasic activity in comparison to total activity: 3 x 10(-8) M 87%, 3 x 10(-6) M 30%) and the neurokinin-2-receptor selective agonist [Nle10]-NKA4-10 (N-NKA: 3 x 10(-8) M 67%, 3 x 10(-6) M 59%) caused both tonic and phasic responses, with the percentage of phasic responses decreasing at higher concentrations. The neurokinin-1-receptor selective agonist [beta Ala4, Sar9, Met(O2)]-SP4-11 caused a predominantly tonic response with only a small phasic component (10(-8) M 27.1% 10(-6) M 13.8%). The selective neurokinin-3 receptor agonist [beta Asp4, MePhe7]-NKB4-10 caused a predominantly phasic motor response (SM-SP: 3 x 10(-8) M 98%, 3 x 10(-6) M 87%). Tetrodotoxin (TTX 10(-6) M), omega-conotoxin (CTX 10(-7) M) and atropine (10(-6) M) had no significant influence on the contractile responses to all four peptides, indicating a direct action on the smooth muscle cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Nitric oxide as putative nonadrenergic noncholinergic inhibitory transmitter in the opossum sphincter of Oddi.

The sphincter of Oddi has a typical nonadrenergic noncholinergic inhibitory innervation; however, the transmitter of this inhibition has not been identified. The aim of the present study was to evaluate whether metabolites of the L-arginine--nitric oxide synthase pathway mediate neural inhibition in the sphincter of Oddi of the opossum. Electrical field stimulation at various frequencies (3, 5, and 10 pulses/s), performed in the presence of guanethidine (10(-6) M) to exclude adrenergic responses, caused a slight, but significant excitatory response of the sphincter of Oddi. The responses were more pronounced at the duodenal side of the sphincter of Oddi than on the hepatic side. When the electrical field stimulation was repeated after blockading muscarinic receptors, using atropine (10(-6) M), a potent inhibitory response was obtained. The inhibitory response to each of the various stimulation parameters was similar. Addition of L-arginine methyl ester (L-NAME, 2 x 10(-4) M) abolished and reversed the inhibitory effect of electrical field stimulation, resulting in a potent stimulatory effect. Higher frequencies (5 and 10 pulses/s) were more potent in causing a stimulatory response than lower frequencies (3 pulses/s). The excitatory effect of electrical field stimulation was blocked or reversed to inhibition when the amino acid L-arginine (2 x 10(-3) M) was added to the bath. In a second series of experiments, the inhibitory effect of electrical field stimulation in the presence of atropine and guanethidine was not prevented after the addition of methylene blue (5 x 10(-5) M), a substance that, in vascular smooth muscle, has been demonstrated to block cyclic GMP dependent inhibitory responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1992

Ascending neural pathways in the rat ileum in vitro--effect of capsaicin and involvement of nitric oxide.

The aim of the present study was to develop and characterize an in vitro model of the rat ileum in which activation of the orally projecting neural excitatory pathway of the myenteric reflex is produced by electrical field stimulation anally to the recording site. The motility of a 10-cm segment of rat ileum was recorded using a perfused manometric assembly with side holes 2 and 4 cm orally to the stimulation site. Electrical field stimulation caused a contractile response in the oral but not in the aboral direction of the stimulation site. The contractile response, which was maximal using low stimulus frequencies (3 or 5 pulses per second (pps)) and decreased with higher frequencies (10 or 20 pps), was blocked by atropine (10(-6) M) at all frequencies tested after acute and after prolonged (greater than 30 min) treatment. The maximal contractile response at 3 pps was abolished by hexamethonium (10(-4) M), tetrodotoxin (5 x 10(-7) M) and by complete transection of the muscular wall between the stimulation and the recording site. Acute administration of capsaicin (8 x 10(-7) M) to the bath reduced the lag between the start of the electrical stimulation and the onset of the contractile response. Higher concentrations of capsaicin (10(-5) M) reduced the contractile response, but this was partly due to an unspecific effect of capsaicin. Blockade of nitric oxide (NO) synthesis by L-NG-nitro-arginine-methyl ester (L-NAME) (3 x 10(-4) M) augmented the contractile response to anal stimulation by 222.4% and reduced the lag period by 54.5%, whereas the stereoisomer D-NAME had no significant effect. The potentiating effects of L-NAME were reversed in the presence of L-arginine (3 x 10(-3) M) but not in the presence of the stereoisomer D-arginine (3 x 10(-3) M). This model can be used to study ascending neural pathways in the rat small intestine. The ascending excitatory response is abolished by atropine and hexamethonium and is modulated by capsicin-sensitive fibers. The ascending pathway is under tonic inhibition of metabolites of the L-arginine-NO pathway.

Analysis of Variance↗
PubMed1992

Aerobilia and hypomotility of the sphincter of Oddi in a patient with chronic intestinal pseudo-obstruction.

A 50-year-old woman with a typical history of chronic idiopathic intestinal pseudo-obstruction was admitted to hospital because of an acute episode of abdominal cramps, nausea, and vomiting. The diagnosis of chronic idiopathic intestinal pseudo-obstruction had been established in this patient who had malnutrition and extreme weight loss as a result of severe malabsorption syndrome. The abdominal roentgenogram showed a typical hypotonic intestine with an enlarged stomach and distended intestinal loops with the radiological signs of an ileus. In addition to former episodes, there was also a transient aerobilia. The patient had not undergone biliary surgery or endoscopic sphincterotomy. To investigate the cause of the findings, endoscopic retrograde cholangiopancreatography and endoscopic manometry of the sphincter of Oddi were performed. The endoscopy showed the stomach and duodenum with a wide and dilated lumen and no spontaneous motility. Endoscopic manometry of the biliary tract and the sphincter of Oddi showed several abnormalities compared with a group of normal volunteers or patients who were examined via biliary manometry for other reasons. There was a low basal pressure (3.5 mm Hg) in the sphincter of Oddi together with low-amplitude phasic contractions (25-30 mm Hg), but the contraction frequency was in the normal range. Further investigations of the motility of the gastrointestinal tract in this patient showed diffuse esophageal spasms and a markedly delayed gastric emptying. The findings of biliary manometry in this patient suggest involvement of the sphincter of Oddi and the biliary system in chronic idiopathic pseudo-obstruction.

Air↗
PubMed1992

Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo.

Antropyloroduodenal motility was recorded in seven anesthetized dogs to assess the role of nitric oxide and L-arginine metabolites in nonadrenergic noncholinergic (NANC) mediation of pyloric relaxation. Pyloric activity induced by duodenal field stimulation was inhibited by antral field stimulation and electrical vagal stimulation. Intra-arterial NG-L-arginine-methyl-ester (L-NAME) reduced the inhibition from antral or vagal stimulation (P less than 0.05). Intravenous infusion of L-NAME also blocked the inhibitory effect of vagal and antral stimulation but left the tetrodotoxin-insensitive action of intra-arterial vasoactive intestinal peptide (VIP) and sodium nitroprusside unchanged. L-Arginine reversed the effect of L-NAME whereas D-arginine did not. L-NAME enhanced pyloric contractions to intra-arterial acetylcholine. The NANC inhibition of the substance P-stimulated pyloric response in vitro was blocked by L-NAME and reversed by addition of L-arginine. Sodium nitroprusside was effective as a relaxant in vitro but VIP was not. These data suggest that metabolites of L-arginine mediate neural inhibition of canine pyloric motor activity.

Animals↗
PubMed1992

Mechanisms of neurotensin-induced inhibition in rat ileal smooth muscle.

The aim of the present study was to determine the mechanisms of neurotensin-induced inhibition in ileal smooth muscle. Isolated rat ileal smooth muscle strips were stimulated in an organ bath using carbachol (CCH) or by KCl depolarization. Neurotensin produced a concentration-dependent inhibition of muscle contraction [mean inhibitory concentration (IC50): 2.8 x 10(-9) M], which was not blocked by phentolamine (10(-6) M), hexamethonium (10(-4) M), indomethacin (10(-6) M), nordihydroguaretic acid (10(-6) M), or tetrodotoxin (10(-6) M). The inhibitory effect of neurotensin during CCH stimulation was blocked concentration dependently in the presence of the K(+)-channel blocker apamin. By contrast, other K(+)-channel blockers such as 9-aminoacridine (10(-6) M to 3 x 10(-5) M), 4-aminopyridine (10(-4) M to 5 x 10(-3) M), tetraethylammonium (10(-4) M to 10(-1) M), or glibenclamide (10(-5) M) were ineffective. The presence of the Ca(2+)-channel antagonist nitrendipine (IC50: 2.4 x 10(-9) M) or verapamil (IC50: 1.1 x 10(-7) M) also blocked the neurotensin inhibitory effect. Ileal contraction, induced by the Ca(2+)-channel activator BAY K 8644 (10(-7) M), was completely inhibited by neurotensin. After depletion of internal Ca2+ stores by repetitive stimulation with CCH and caffeine in Ca(2+)-free buffer, reintroduction of external Ca2+ restored neurotensin inhibition of the contraction induced by CCH. These results demonstrate that the inhibitory effect of neurotensin in rat ileum longitudinal muscle is apamin sensitive and cannot be observed in the presence of the Ca(2+)-channel blockers nitrendipine or verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Sensory nerves of the intestines: role in control of pyloric region of dogs.

The canine pylorus is the target for a large array of extrinsic and intrinsic nerve-produced effects. Some of them have intermediate nicotinic synapses. In all cases observed so far the final nerve terminals mediating excitation are cholinergic, but those mediating inhibition are both adrenergic and non-adrenergic non-cholinergic. The role of the dense peptidergic innervation is unclear especially in view of the observation that this muscle and its nerves contain receptors to all of those studied (VIP, PHI, GAL, SP, NKA, NKB, CCK, and others. The pylorus is also the target of an important reflex initiated by acid in the duodenal lumen. Our preliminary work suggests that this reflex is initiated by acid induced release of 5HT from the EC cells to act on 5HT receptors on sensory nerves which activate the ascending chain of cholinergic nerves in the myenteric plexus. This same stimulus may also activate other vagal sensory nerves.

Animals↗
PubMed1991

Alpha 2-adrenergic receptors on the circular smooth muscle of canine small intestine.

We have studied the distribution and properties of alpha 2-adrenergic receptors in the circular muscle layer (containing deep muscular plexus) of canine small intestine. Using radioactivity labelled rauwolscine, we located the binding sites to the neuronal membranes supporting the prejunctional action of alpha 2-adrenergic agents in the gut. Moreover, although the functional data to suggest the existence of postjunctional alpha 2-adrenergic receptors coupled to contraction are not available so far, we measured a substantial number of rauwolscine binding sites on the smooth muscle plasma membranes. Scatchard and Hill analyses of the saturation data were indicative of the presence of a single high affinity site (Hill coefficient 0.996) with a KD value of 8.8 nM and the maximum number of binding sites (Bmax) of 313 fmol/mg of protein. Competition studies suggested the presence of multiple subtypes of alpha 2-adrenoceptors.

Animals↗
PubMed1991

Modulatory effect of insulin on rat small intestinal motility and peptide release in vitro.

Intact segments of rat ileum were stimulated in vitro by either electrical field stimulation (EFS) or cholinergic stimulation with carbachol, in the presence of absence of varying insulin concentrations (50, 100 and 200 microU/ml), and the contraction in the longitudinal axis was recorded. Insulin had no significant influence on the carbachol contractile dose-response curve nor did it affect the cholinergically mediated 'on-contraction' at onset of the electrical stimulus. The 'off-contraction' occurring at cessation of the electrical stimulus was partly mediated by a cholinergic and partly by a noncholinergic and nonadrenergic mechanism, and decreased over time with repeated stimulation. This decay with time was significantly attenuated by insulin. In the presence of insulin, release of bombesin-like immunoreactivity induced by carbachol or EFS significantly increased. On the other hand, the release of somatostatin-like immunoreactivity was suppressed by 50-70% in the presence of insulin. These results demonstrate that in vitro insulin can modify both the motility responses of isolated segments of rat ileum and the neuropeptide release from such segments.

Animals↗
PubMed1991

Effect of motilin on gastric emptying in patients with diabetic gastroparesis.

OBJECTIVES: Because disturbances of gastric emptying are a serious complication in insulin-dependent diabetic subjects with regard to the maintenance of good metabolic control, we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances. RESEARCH DESIGN AND METHODS: The intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects. Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis. All patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects. RESULTS: During the infusion of motilin, gastric emptying was accelerated, and it was no longer significantly different from control values. CONCLUSIONS: These data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects.

Adult↗
PubMed1991

[Medicamentous modification of gastrointestinal motility and secretion].

This article gives an overview on possible new pharmacological tools to modify gastrointestinal motility and/or secretion. The characterization of new subclasses of classical neurotransmitter receptors and of peptidergic receptors offer a new approach for the development of new therapeutic agents. Using molecular biology techniques a variety of receptor subclasses have been demonstrated for muscarinic and alpha 2-adrenergic receptors. Both receptor types are of major importance for the regulation of mucosal secretion in the submucosal plexus and specific ligands for these receptor subtypes could be of clinical interest. In the next paragraphs the possible therapeutic relevance of 5-HT3-receptor antagonists and of opiate agonist and -antagonists is discussed. 5-HT3-antagonists, which can be used as potent antiemetics, also demonstrate quite potent effects on upper gastrointestinal motility such as gastric emptying. Whereas the subclassification of opioids has so far no specific therapeutic consequences there is some evidence that casomorphin, a derivative of the casein of the milk, could be used as a possible antidiarhoic substance. The use of antagonist and agonists on peptidergic receptors with orally active ligands offer a further new therapeutic approach. This is discussed for CCK-antagonists and erythromycin-analogues which are agonists at the motilin receptor. Besides this experimental approach to modify defined receptor subclasses, there are new substances with so far not clearly defined mechanism of action, which, however, have potent therapeutic effects. Cisapride, a new potent prokinetic drug with little side effects, is now available for clinical use for a wide range of motility disorders.

Digestive System↗
PubMed1991

Interaction of trimebutine and Jo-1196 (fedotozine) with opioid receptors in the canine ileum.

Receptor binding of the opioid receptor antagonist, [3H]diprenorphine, which has a similar affinity to the various opioid receptor subtypes, was characterized in subcellular fractions derived from either longitudinal or circular smooth muscle of the canine small intestine with their plexuses (myenteric plexus and deep muscular plexus, respectively) attached. The distribution of opioid binding activity showed a good correlation in the different fractions with the binding of the neuronal marker [3H]saxitoxin but no correlation to the smooth muscle plasma membrane marker 5'-nucleotidase. The saturation data (Kd = 0.12 +/- 0.04 nM and maximum binding = 400 +/- 20 fmol/mg) and the data from kinetic experiments (Kd = 0.08 nmol) in the myenteric plexus were in good agreement with results obtained previously from the circular muscle/deep muscular plexus preparation. Competition experiments using selective drugs for mu [morphiceptin-analog (N-MePhe3-D-Pro4)-morphiceptin] ), delta (D-Pen2,5-enkephalin) and kappa (dynorphin 1-13, U50488-H) ligands showed the existence of all three receptor subtypes. The existence of kappa receptors was confirmed in saturation experiments using [3H] ethylketocycloazocine as labeled ligand. Two putative opioid agonists, with effects on gastrointestinal motility, trimebutine and JO-1196 (fedotozin), were also examined. Trimebutine (Ki = 0.18 microM), Des-Met-trimebutine (Ki = 0.72 microM) and Jo-1196 (Ki = 0.19 microM) displaced specific opiate binding. The relative affinity for the opioid receptor subtypes was mu = 0.44, delta = 0.30 and kappa = 0.26 for trimebutine and mu = 0.25, delta = 0.22 and kappa = 0.52 for Jo-1196. Thus, Jo-1196 had some selectivity for kappa receptors compared to trimebutine. We conclude that there are similar types of opioid receptors in the myenteric plexus and the deep muscular plexus and that specificity of function of opioid nerves must depend on differential location of receptor types on particular neurons. The action of trimebutine and related drugs could vary depending upon their interactions with various gut opioid receptors having different physiological roles.

5'-Nucleotidase↗
PubMed1990

Effect of N-butylscopolamine on sphincter of Oddi motility in patients during routine ERCP--a manometric study.

N-butylscopolamine is a generally accepted drug for the suppression of gut motility. Although it is used during routine ERCP, only few systematic studies have been carried out in patients to investigate its action on sphincter of Oddi motility. In the present study the effect of N-butylscopolamine on the motility of the sphincter of Oddi region has been evaluated in 17 patients undergoing routine diagnostic ERCP. The pressure parameters of these patients were compared with "normal values" obtained in 23 volunteers. A dose of 40 mg of N-butylscopolamine bromide (Buscopan) i.v. significantly reduced the contraction frequency of the sphincter of Oddi from 5.4 +/- 1.2/min to 1.0 +/- 1.4/min (p less than 0.001), the contraction amplitude from 106.3 +/- 27.8 mmHg to 55.2 +/- 23.5 (p less than 0.01) mmHg, and the basal sphincter of Oddi pressure from 13.9 +/- 3.0 mmHg to 11.0 +/- 3.5 mmHg (p less than 0.05), but had no effect on the pressure gradient between the common bile duct and the duodenum. These results clearly demonstrate that N-butylscopolamine inhibits contractions of the sphincter of Oddi, and may thus facilitate the intubation of the papilla.

Adult↗
PubMed1990

[Systemic candidiasis in intensive care patients after antibiotic therapy].

The authors report fluconazole treatment of 19 I.C.U. patients in critical situations. 9 of these patients had septic multiorgan failure. All patients had received long term antibiotic treatment for at least seven days. The difficulties in clinical and laboratory diagnosis of systemic candidosis which requires treatment are discussed. All patients showed good response to fluconazole treatment concerning the opportunistic mycotic infection; none of the patients died because of systemic candidosis. Severe side effects were not observed.

Anti-Bacterial Agents↗