This review gives a historical perspective, summarizing approximately 25 years of research on opioids. The "typical" opioid peptides produced in the brain, "atypical" opioids encrypted in milk protein or hemoglobin sequences, and extremely potent and selective opioids of amphibian origin are described. The main focus is on the structure-activity relationship studies of peptide ligands for three main opioid receptor types (micro, delta, kappa), their selectivities and pharmacological activities in vitro. Chemical modifications that led to obtaining potent and selective agonists and antagonists for these receptors are discussed.

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A proper diet is one of major factors contributing to good health and is directly related to general condition of the organism. Phenolic compounds are abundant in foods and beverages (fresh and processed fruits and vegetables, leguminous plants, cereals, herbs, spices, tea, coffee, wine, beer) and their pleiotropic biological activities result in numerous health beneficial effects. On the other hand, high reactivity and very large diversity in terms of structure and molecular weight renders polyphenols one of the most difficult groups of compounds to investigate, as evidenced by ambiguous and sometimes contradictory results of many studies. Furthermore, phenolics undergo metabolic transformations, which significantly change their biological activities. Here, we discuss some aspects of metabolism and absorption of phenolic compounds. On the basis of information reported in the literature as well as in summaries of clinical trials and patent applications, we also give an overview of strategies for enhancing their bioavailability.

Somatostatin is a hypothalamic peptide hormone that inhibits the secretion of growth hormone, glucagon, insulin, gastrin and secretin, and also plays a role in neural transmission. Because of its wide range of possible clinical applications hundreds of somatostatin analogs have been synthesized and bioassayed to date. This review gives a historical perspective, summarizing approximately 30 years of research on somatostatin. The main focus is on the structure-activity relationships and conformational studies of the last generation of somatostatin agonists and their selectivity for five somatostatin receptor subtypes. Achievements in the synthesis of nonpeptide somatostatin analogs, as well as the first somatostatin antagonists, are also discussed. Finally, the use of a cyclic somatostatin scaffold to design ligands for other G-protein-coupled receptors, such as opioid and melanocortin receptors, is mentioned.

The major active ingredient of the plant Salvia divinorum, salvinorin A (SA) has been used to treat gastrointestinal (GI) symptoms. As the action of SA on the regulation of colonic function is unknown, our aim was to examine the effects of SA on mouse colonic motility and secretion in vitro and in vivo. The effects of SA on GI motility were studied using isolated preparations of colon, which were compared with preparations from stomach and ileum. Colonic epithelial ion transport was evaluated using Ussing chambers. Additionally, we studied GI motility in vivo by measuring colonic propulsion, gastric emptying, and upper GI transit. Salvinorin A inhibited contractions of the mouse colon, stomach, and ileum in vitro, prolonged colonic propulsion and slowed upper GI transit in vivo. Salvinorin A had no effect on gastric emptying in vivo. Salvinorin A reduced veratridine-, but not forskolin-induced epithelial ion transport. The effects of SA on colonic motility in vitro were mediated by kappa-opioid receptors (KORs) and cannabinoid (CB) receptors, as they were inhibited by the antagonists nor-binaltorphimine (KOR), AM 251 (CB(1) receptor) and AM 630 (CB(2) receptor). However, in the colon in vivo, the effects were largely mediated by KORs. The effects of SA on veratridine-mediated epithelial ion transport were inhibited by nor-binaltorphimine and AM 630. Salvinorin A slows colonic motility in vitro and in vivo and influences neurogenic ion transport. Due to its specific regional action, SA or its derivatives may be useful drugs in the treatment of lower GI disorders associated with increased GI transit and diarrhoea.

Recent reports suggested that the activation of Transient Receptor Potential Vanilloid 4 (TRPV4) receptors in the gastrointestinal tract has pro-inflammatory effects. In this study, we demonstrated for the first time that TRPV4 mRNA expression is up-regulated in patients with inflammatory bowel diseases (IBD). Furthermore, selective blockade of TRPV4 in the 2,4,6-trinitrobenzenesulfonic acid animal model alleviates colitis and pain associated with the intestinal inflammation. Our study indicates that TRPV4 may play a role in mechanisms of defense in intestinal inflammation and that TRPV4 may be an attractive target for future systemic or topic anti-inflammatory treatment in patients with IBD.

Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases.