Luminary Learning Gastrointestinal Disorder- Issue 1

14  • LUMINARY LEARNING: GASTROINTESTINAL DISORDERS ClC Chloride ion channels CFTR Cystic fibrosis transmembrane conductance regulator CC Chronic constipation CIC Chronic idiopathic constipation IBS-C Constipation-predominant irritable bowel syndrome DPP IV Dipeptidyl peptidase IV ECS Endocannabinoid system EOS Endogenous opioid system GI Gastrointestinal GC-C Guanylate cyclase C HEK cells Human embryonic kidney cells EC cells Enterochromaffin cells 5-HT Serotonin SERT Serotonin-selective reuptake transporter SCBM Spontaneous complete bowel movement TPH1/2 Tryptophan hydroxylase 1/2 5-HT2B Type 2B serotonin receptor 5-HT3 Type 3 serotonin receptor 5-HT4 Type 4 serotonin receptor Introduction Irritable bowel syndrome (IBS) is a complex and multifactorial disease with multiple molecular mechanisms involved in its pathophysiology. Consequently, the exact mechanism responsible for the development of IBS remains unrevealed what significantly hinders the search for the new medications. Nevertheless meaningful efforts have been put on the development of drugs that secure fundamental therapeutic goals of the treatment of IBS, such as improvement of unbear- able symptoms accompanied with augmentation of patients quality of life. Intensive research in this field lead to the development of several treatment options tailored to the specific groups of patients based on the type of IBS or gender (please see below for more details). Since IBS is not accompanied with any known organic changes in the gut, and none of these treatment options includes invasive procedures, the IBS patients must rely solely on the pharmacotherapy and life- style modification. Of note, the present-day prospect of anti-IBS therapies as well as drugs avail- able on the market undergoes constant variations with some compounds being withdrawn and other ones entering it in a relatively short time span. In this chapter we provide an overview on the pharmacological targets for small-molecule anti-IBS drugs including serotonin receptors, chloride ion channels, guanylate cyclase C (GC-C), endogenous opioid system (EOS), cystic fibrosis transmembrane conductance regulator (CFTR) and somatostatin-2 receptors (Fig. 1). We also discuss the virtues and drawbacks of the most com- monly prescribed medications. Moreover, we introduce selected complementary and alternative medicine (CAM) methods that have been proven effective in clinical tests.