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
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.