摘要:

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.

ISSN:0012-2823    

DOI:10.1159/000200658

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Both human and guinea pig gallbladder strips were tonically contracted by supramaximal concentrations of histamine in vitro. Guinea pig gallbladder strips were also tonically contracted by potassium, with no spontaneous relaxation after 5 min. The amplitude of the contractions caused by histamine decreased spontaneously only by 34 ± (SD) 10% after 5 min in guinea pig strips and by 25 ± 7% after 5 min in human strips. Both oxytocin and 8-l-lysine-vasopressin dose-dependently relaxed almost completely contractions caused by histamine and potassium in guinea pigs. In humans, only 8-l-lysine-vasopres-sin decreased the amplitude of histamine contractions. In both species, neither oxytocin nor 8-l-lysine-vasopressin affected the basal tone of strip

ISSN:0012-2823    

DOI:10.1159/000200659

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The purpose of this study was to clarify the involvement of adenine nucleotide metabolism and substrates of the xanthine-xanthine oxidase system as the source of oxygen free radicals in a rat model of restrained water immersion stress ulceration. The gastric mucosal concentrations of adenine-5’-triphosphate (ATP), adenine-5´-diphosphate (ADP), adenine-5´-monophosphate (AMP) and thiobarbituric-acid (TBA)-reactant substances were measured after 4, 8 and 12 h restrained water immersion stress. The gastric mucosal concentrations of the nucleoside adenosine, the purine bases xanthine and hypoxanthine, and the final metabolic product uric acid, were measured after 4 h of restrained water immersion stress. The concentrations of ATP diminished significantly after 4, 8 and 12 h of restrained water immersion stress. However, the observed stress-induced changes in ADP were not significant. AMP concentrations increased significantly after 4, 8 and 12 h of stress. The adenylate pool (ATP + ADP + AMP) dropped significantly from the prestress value after 4, 8 and 12 h of stress, and the concomitant energy charge (EC = ATP + 0.5 ADP/ATP + ADP+ AMP) decreased significantly after 4 and 8 h of stress compared with the prestress value. Gastric mucosal concentrations of TBA-reactant substances displayed a significant increase after 4 h of stress, and remained unchanged after 8 and 12 h of stress from the level after 4 h. Four hours of restrained water immersion stress induced an increase in adenosine and uric acid concentrations and a decrease in the hypoxanthine concentration of the gastric mucosa. In addition, the protective effect of tetraprenylacetone (TPA) with respect to energy metabolism impairment and the production of active oxygen was investigated. Administration of TPA inhibited the ulcer formation, the reduction in energy charge values after 4 and 8 h of restrained water immersion stress and the increase in TBA-reactant substances after 4 h of restrained water immersion stress. TPA administration also inhibited the increase in adenosine and uric acid concentrations as well as the decrease in the hypoxanthine concentrations of the gastric mucosa caused by restrained water immersion stress. These results suggest that TPA exerted a cytoprotective action by virtue of its ability to counteract the adenine nucleotide metabolism and its action on the substrates of the xanthine-xanthine oxidase sys

ISSN:0012-2823    

DOI:10.1159/000200660

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In conscious dogs with gastric and pancreatic fistulas, we compared the action of different doses of telenzepine (ranging from 9 to 243 nmol kg-1 h-1 i.v.) and pirenzepine (ranging from 43 to 1,170 nmol kg-1 h-1 i.v.) on the pancreatic secretory response to graded loads of intraduodenal infusions of tryptophan, given with a secretin background. Both, telenzepine and pirenzepine caused an overall significant inhibition of the cumulative incremental pancreatic protein output by 65.8 and 66.8%, respectively. The pancreatic bicarbonate output was also reduced by 38.3 and 40.5%, respectively, but the effect did not reach statistical significance. The inhibitory potency of the effective doses of telenzepine or pirenzepine did not differ significantly. Only the highest doses of telenzepine (243 nmol kg-1 h-1 i.v.) and of pirenzepine (1,170 nmol kg-1 h-1 i.v.) significantly increased heart rate from 59.9 ± 3.4 to 63.1 ± 4.5 bpm, respectively. These findings indicate that (1) in the intact animal, the M1-receptor antagonists telenzepine and pirenzepine are capable of inhibiting pancreatic bicarbonate and protein output in response to intraduodenal tryptophan with secretin background, and (2) telenzepine is 4.7 times more potent than pirenzepin

ISSN:0012-2823    

DOI:10.1159/000200661

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Treatment with sodium-channel-blocking agents is accompanied by a high incidence of gastrointestinal side effects. We therefore studied the influence of two sodium channel blockers, mexiletine and flecanaide, on gastric and jejunal myoelectrical activity of unanesthetized rats. Bipolar electrodes were implanted chronically on the serosal surface of the antrum or the jejunum of male rats (weight: 250–350 g). Electrical activity was recorded on a Polygraph starting on day 5 after the operation. After 1 h of baseline recordings, either vehicle or an active drug was given randomly. Recordings were continued for 4 h after drug administration. Vehicle did not induce changes in slow-wave frequency. In contrast, gastric slow-wave activity significantly decreased after the administration of both mexiletine and flecanaide. Jejunal myoelectrical activity was only slightly affected by sodium channel blockade. The disruption of gastric myoelectrical activity may contribute to the side effects observed during chronic treatment with class I antiarrhythmic drug

ISSN:0012-2823    

DOI:10.1159/000200662

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Oligofecorrhea is the term applied for infrequent defecation (2 or less stools per week). 146 patients with oligofecorrhea were studied. Investigations comprised radiologic, endoscopic, intestinal transit and rectal pressure studies. EMG for levator and sphincteric muscles as well as internal sphincter biopsy were done. The 146 patients could be categorized into 3 stages according to clinical and investigative results. However, the 3 stages share major abnormal findings which comprise high resting rectal neck pressure, reduced or absent recto-inhibitory reflex, internal sphinter hypertrophy and degeneration of the nerve plexus of the internal sphincter. A new theory of pathogenesis of oligofecorrhea is put forward. It is believed that innervation abnormalities of the internal sphincter interferes with the recto-inhibitory reflex action with a resulting failure of the internal sphincter to relax upon rectal distension. It seems that the degenerative changes of the nerve plexus affect mainly the parasympathetic supply leading to sympathetic overactivity. The latter leads to abnormal internal sphincter contraction which eventually results in muscle hypertrophy. Internal sphincter myotomy showed a mean improvement of 90.4% in all the cases. The stool frequency and rectal neck pressure were normalized.

ISSN:0012-2823    

DOI:10.1159/000200663

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000200664

出版商:S. Karger AG    

年代:1991

数据来源: Karger