{"id":565,"date":"2026-02-25T11:41:14","date_gmt":"2026-02-25T10:41:14","guid":{"rendered":"https:\/\/5-ht7r.org\/?page_id=565"},"modified":"2026-02-25T11:41:14","modified_gmt":"2026-02-25T10:41:14","slug":"physiology-disorders","status":"publish","type":"page","link":"https:\/\/5-ht7r.org\/?page_id=565","title":{"rendered":"Physiology\/disorders"},"content":{"rendered":"<style>\r\n\t.item {\r\n\t\tbackground-color:var(--global-color);\r\n\t\tcolor: white;\r\n    \tpadding: 14px 32px;\r\n    \tborder: none;\r\n    \tborder-radius: 25px;\r\n    \tfont-size: 1em;\r\n    \tcursor: pointer;\r\n    \ttransition: all 0.3s;\r\n    \tbox-shadow: 0 4px 15px rgba(0, 0, 0, 0.1);\r\n    \tfont-weight: 500;\t\t\r\n\t}\r\n\t.item:hover {\r\n\t\tbackground-color: lightblue;\r\n\t\tcolor: black;\r\n\t}\r\n\r\n<\/style>\r\n<div style=\"display:flex;flex-direction:row;justify-content:space-around\">\r\n\t<p class=\"item\" attrib=\"CNS_disorders\" style=\"background:lightblue\">Neurosciences<\/p>\r\n    <p class=\"item\" attrib=\"Cardiovascular_system\" >Cardiovascular system<\/p>\r\n    <p class=\"item\" attrib=\"Gastrointestinal_tract\" >Gastrointestinal tract<\/p>\r\n    <p class=\"item\" attrib=\"Immune_system\">Immune system<\/p>\r\n<\/div>\r\n<div>\r\n\t<p class=\"paragraphe\" id=\"CNS_disorders\" style=\"display:block\">\t\r\n\tIn addition to its role as neurotransmitter, 5-HT exerts morphogenic actions and controls neurodevelopmental processes such as neurogenesis, axon guidance, dendritogenesis, synaptogenesis, cell migration and brain wiring [26, 27]. The 5-HT<sub>7<\/sub>R has become a promising target for the treatment of neuropsychiatric and neurologic disorders; this is evidenced by the numerous 5-HT<sub>7<\/sub>R antagonist drug discovery programs across the world [14]. Increasing data regarding the expression profiles of 5-HT<sub>7<\/sub>R show that it contributes to the establishment and remodeling of neuronal cytoarchitecture during brain development. Therefore, dysfunction or modulation of 5-HT<sub>7<\/sub>R is linked to the pathogenesis\/pathophysiology of neurodevelopmental disorders. In the adult, 5-HT<sub>7<\/sub>R stimulates synaptic plasticity which, in turn, affects many physiological functions such as learning, memory, mood and reward. Therefore, the 5-HT<sub>7<\/sub>R is also a target in the adult, as it could influence mood disorders, schizophrenia, and other cognitive disturbance disorders [28, 29 , 30]. However, the pharmacological and genetic manipulation of 5-HT<sub>7<\/sub>R in animal models of depression, anxiety, schizophrenia, neuropathic pain has often given inconsistent or conflicting results. Experimental conditions such as difference in animal\u2019s strain, behavioral tests, drugs and their doses, route of administration as well as the use of non-selective drugs have to be taken in consideration. A new level of complexity is added with the notion of biased ligands which could affect transmission and intracellular signaling systems in a different way from classical ligands. Biased agonism of test drugs could account, at least in part, for these discordant results. By gathering experts and information around these results\/studies, the proposed consortium aims to understand the basis of these complexities and provided a clearer path forward by working together. \r\n\t<\/p> \r\n\t<p class=\"paragraphe\"  id=\"Cardiovascular_system\" style=\"display:none\">\t\r\n\t5-HT7R stimulation, as mediated by medial smooth muscle, results in vascular relaxation. This is true for large veins [31] and small arterioles [32] in vitro and occurs through activation of the 5-HT<sub>7<\/sub>R. In vivo, administration of a low dose of 5-HT causes a hypotension that can last up to a month during administration [33]. Importantly, the hypotension mediated by 5-HT is abolished in the presence of pharmacological blockade by SB269970 [34] or genetic loss of the 5-HT<sub>7<\/sub>R in the rat [35]. What is unknown at this point is how the 5-HT<sub>7<\/sub>R functions in vivo to carry out these effects. Specifically, is a subset of receptors recruited to stimulate Gs to elicit the hypotension; to stimulate \u03b2-arrestin to elicit the hypotension, or is a balance of both necessary? Our published collaborative work suggests that a Gs biased, not \u03b2-arrestin-biased, 5-HT<sub>7<\/sub>R ligand would be a beneficial type of drug to develop for treatment of elevated blood pressure (hypertension) or diseases that benefit from a lowering of blood pressure (heart failure). Thus, cardiovascular research, like CNS disorders described above, will benefit from a consortium of researchers that can gather or discover, as Dr. Morisset-Lopez, Dr. Suzenet and Dr. Watts did with serodolin, the right\/best tools to answer these important questions and test important ideas. \t\t\r\n\t<\/p>\r\n\t<p class=\"paragraphe\"  id=\"Gastrointestinal_tract\" style=\"display:none\">\t\r\n\tThe vast majority of 5-HT is detected in the gastrointestinal epithelium and is produced by enterochromaffin cells of the gut mucosa. The 5-HT<sub>7<\/sub>R contributes in generation\/perturbation of intestinal inflammation [36]. 5-HT<sub>7<\/sub>R expression is significantly increased in inflamed intestinal dendritic cells of patients with Crohn\u2019s disease as well as in an experimental murine models of inflammatory bowel disease such as DSS-induced colitis [37]. However, the testing of the involvement of 5-HT<sub>7<\/sub>R in pathological gastrointestinal functions has produced contradictory results that depend on the experimental model used. Specifically, pharmacological antagonism or genetic ablation of 5-HT<sub>7<\/sub>R resulted in increased severity of symptoms in both acute and chronic mouse models of colitis. Consistent with the 5-HT<sub>7<\/sub>R endogenously restraining the pathology of this disease, activation of the receptor by agonists produced an anti-inflammatory effect [38]. In stark contrast, Kim and collaborators showed that genetic or pharmacological silencing of 5-HT7R reduced the severity of intestinal inflammation after induction of colitis in mice [39]. As in CNS disorders and CV disease described above, the consortium could help understanding these contradictory results by gathering the experts and information around the 5-HT<sub>7<\/sub>R (proposed below).\r\n\t<\/p>\r\n\t<p class=\"paragraphe\"  id=\"Immune_system\" style=\"display:none\">\t\r\n\tThe connection between 5-HT<sub>7<\/sub>R and inflammation is still limited but is consistently being advanced by the field. 5-HT<sub>7<\/sub>R is expressed on the surface of major actors of the peripheral immune response such as T-lymphocytes, macrophages and dendritic cells [40]. The 5-HT<sub>7<\/sub>R has recently detected on T regulatory cells infiltrated into the brain after ischaemic stroke [41]. However, 5-HT<sub>7<\/sub>R have diverse and even inconsistent roles in the immune response. This is likely due at least to its expression on different types of immune cells, effecting significantly different endpoints. For example, activation of the 5-HT<sub>7<\/sub>R can be pro-inflammatory: activation of the 5-HT<sub>7<\/sub>R in lymphocytes increases cell proliferation rate [42]. Similarly, in dendritic cells, 5-HT<sub>7<\/sub>R activation induces the secretion of proinflammatory cytokines IL-1\u03b2 and IL-8. By contrast, in monocytes 5-HT<sub>7<\/sub>R activation results in either pro- or anti-inflammatory actions <span class='tooltipsall tooltipsincontent classtoolTips14'>[7]<\/span>. These conundrums can be well addressed by gathering the information and experts to understand the basis for these apparent discrepancies. \t\t\r\n\t<\/p>\r\n\t<p class=\"paragraphe\"  id=\"Cancers\" style=\"display:none\">\t\r\n\t\t\r\n\t<\/p>\r\n\t\r\n<\/div>\r\n\r\n\r\n<script>\r\n\tdocument.querySelectorAll(\".item\").forEach(elem=> {\r\n\t\telem.addEventListener(\"click\",function() {\r\n\t\t\tdocument.querySelectorAll(\".paragraphe\").forEach(Par=> Par.style.display=\"none\");\r\n\t\t\tdocument.querySelectorAll(\".item\").forEach(raz=>raz.style.background=\"#045cd8\");\r\n\t\t\tconst para = elem.getAttribute(\"attrib\");\r\n\t\t\tdocument.getElementById(para).style.display=\"block\";\r\n\t\t\tthis.style.background=\"lightblue\";\r\n\t\t});\r\n\t})\r\n\t\r\n<\/script>\r\n\r\n<script type=\"text\/javascript\"> toolTips('.classtoolTips14','Quintero-Villegas A and S I Valdes-Ferrer, Role of 5-HT7 receptors in the immune system in health and disease<em>.\u00a0<\/em>Mol Med,\u00a0<strong>2019<\/strong>. 26(1), 2'); <\/script>","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-565","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/pages\/565","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/5-ht7r.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=565"}],"version-history":[{"count":1,"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/pages\/565\/revisions"}],"predecessor-version":[{"id":566,"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/pages\/565\/revisions\/566"}],"wp:attachment":[{"href":"https:\/\/5-ht7r.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=565"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}