Characterization of a novel and selective V1B receptor antagonist
| Autor: | Rachel Milne, Mark Craighead, Fiona Thomson, Hugh M. Marston, Leigh Campbell-Wan, Jeremy Presland, Lynn Watson, Cliona P MacSweeney |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Arginine vasopressin receptor 1B
endocrine system medicine.medical_specialty Vasopressin medicine.drug_class Chemistry Adrenocorticotropic hormone Receptor antagonist Endocrinology medicine.anatomical_structure Anterior pituitary Internal medicine Arginine vasopressin receptor 2 medicine ACTH receptor hormones hormone substitutes and hormone antagonists Vasopressin receptor |
| Popis: | It has been argued that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a major biological abnormality in patients suffering from psychiatric conditions such as major depression. Both arginine vasopressin (AVP) and corticotrophin releasing factor (CRF) are responsible for stimulating the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. CRF is thought to be the predominant secretagogue under normal conditions but AVP may play a more important role in situations of aberrant/chronic stress. Studies in patients suffering from melancholic depression indicate a hyper-responsiveness to agonism at the vasopressin receptor type 1B (V1B); patients display a heightened ACTH release after challenge with the mixed V1B/V2 (vasopressin receptor type 2) agonist desmopressin in comparison to control subjects. A V1B antagonist has been developed which has significant selectivity for the human V1B receptor over the other members of the vasopressin receptor sub-family. The compound acts as an effective antagonist at both the human recombinant receptor (stably expressed in Chinese hamster ovary (CHO) cells) and the native rat V1B receptor (using isolated anterior pituitary cells), blocking the induction of luciferase and the release of ACTH, respectively. In vivo the compound can block the release of ACTH after challenge with a variety of V1B agonists. It can also attenuate the ACTH response to acute stressors in rats. Interestingly, this compound does not modulate the activity of the HPA axis under normal basal conditions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|