The purpose of this study was to elucidate the intestinal serotonin (5-HT) receptor subtypes involved in fluid transport in the pig jejunum in uioo. The fluid accumulating effect of intraluminally administered 5-HT, renzapride, methysergide, ketanserin, granisetron, citalopram and intravenous indomethacin, was tested in tied- off loops in uiuo. 5-HT caused a dose-dependent fluid accumulation, which was reduced by indomethacin by about 30 %. Renzapride, methysergide, ketanserin, granisetron and citalopram all caused fluid accumulation. Taking into account these fluid accumulating effects, renzapride, methysergide, ketanserin and granisetron reduced the fluid accumulating effect of 5-HT, giving a maximal reduction of 70, 46, 76, and 80 %, respectively. These data suggest the existence of intestinal 5-HT receptor subtypes involved in fluid transport in the pig jejunum. The antagonistic effects of indomethacin, ketanserin and granisetron, suggest the involvement of prostangladins, as well as the 5-HT2 and the 5-HT3 receptor subtypes in the fluid accumulating response of 5-HT.
Neurohumoral substances and their receptors play a major part in the complex regulation of gastrointestinal motility and have therefore been the predominant targets for drug development. The numerous receptors involved in motility are located mainly on smooth muscle cells and neuronal structures in the extrinsic and intrinsic parts of the enteric nervous system. Within this system, receptor agonists and antagonists interacts directly to modify excitatory or inhibitory signals. In view of this complexity it is not surprising that our knowledge about the mechanisms of actions of the various neurohormones and drugs affecting gut motility has been rather fragmented and incomplete. However, recently substantial progress has been achieved, and drug therapy for gut dysmotility is emerging, based primarily on neurohumoral receptors. This paper presents a selective review of the neurohumoral regulatory mechanisms of gastrointestinal motility. In this context, the physiology and pharmacology of the smooth muscle cells, gastrointestinal motility and dysmotility, the enteric nervous system, gastrointestinal reflexes, and serotonin is presented. Further investigation and understanding of the transmitters and receptors involved in especially the reflex activation of peristalsis is crucial for the development of novel therapies for motility disorders., M. B. Hansen., and Obsahuje bibliografii
This review presents recent findings regarding the physiological and pathophysiological extra- and intracellular mechanisms of secretory diarrhoea. Putative interventions directed towards counteracting the mechanisms causing fluid loss, especially in relation to the enteric nervous system, intracellular mediators, and localization of fluid and electrolyte transport, are discussed. The enteric nervous system regulates the complex process of transmural fluid and electrolyte transport by controlling the function of the mucosa, the motility, and the microcirculation in both health and disease. Most of the processes, leading to secretory diarrhoea, involve activation of the enteric nervous system, with local release of neurotransmitters and other endogenous effectors, which induce chloride secretion. A new therapeutic approach is based on stimulation of absorption and inhibition of secretion by using receptor agonists and antagonists, and modulators of intracellular signal transduction. A physio-pharmacological review of serotonin and the antisecretory factor as modulators of intestinal fluid and electrolyte transport is given.
The mesenteric and intestinal blood flow is organized and regulated to support normal intestinal function, and the regulation of blood flow is, in part, determined by intestinal function itself. In the process of the development and adaptation of the intestinal mucosa for the support of the digestive processes and host defense mechanisms, and the muscle layers for propulsion of foodstuffs, a specialized microvascular architecture has evolved in each tissue layer. Compromised mesenteric and intestinal blood flow, which can be common in the elderly, may lead to devastating clinical consequences. This problem, which can be caused by vasospasm at the microvascular level, can cause intestinal ischaemia to any of the layers of the intestinal wall, and can initiate pathological events which promote significant clinical consequences such as diarrhea, abdominal angina and intestinal infarction. The objective of this review is to provide the reader with some general concepts of the mechanisms by which neurohumoral vasoactive substances influence mesenteric and intestinal arterial blood flow in health and disease with focus on transmural transport processes (absorption and secretion). The complex regulatory mechanisms of extrinsic (sympathetic-parasympathetic and endocrine) and intrinsic (enteric nervous system and humoral- endocrine) components are presented. More extensive reviews of platelet function, atherosclerosis, hypertension, diabetes mellitus, the carcinoid syndrome, 5-hydroxytryptamine and nitric oxide regulation of vascular tone are presented in this context. The possible options of pharmacological intervention (e.g. vasodilator agonists and vasoconstrictor antagonists) used for the treatment of abnormal mesenteric and intestinal vascular states are also discussed.
Gastrointestinal motility is an integrated process including myoelectrical and contractile activity, tone, compliance and transit. The techniques for the assessment of gastrointestinal motility are multiple and all have their advantages and disadvantages. In the case of suspected abnormal upper gut transit, gastric and small bowel transit scintigraphy followed by small intestinal (antroduodenojejunalileal) manometry is recommended. Small bowel manometry can identify patterns suggestive of myopathy, neuropathy or obstruction. Information on procedures, indications, significance, pitfalls and guidelines for small bowel manometry is provided in this paper. In this context the potentials of small intestinal manometry for scientific experimental study of neurohumoral agents, such as serotonin receptor agonists and antagonists, on small intestinal motility is presented., M. B. Hansen., and Obsahuje bibliografii