[1-Deamino-4-Cyclohexylalanine] Arginine Vasopressin: A Potent and Specific Agonist for Vasopressin V1b Receptors
| Autor: | Hazel H. Szeto, Stoytcho Stoev, Sylvain Derick, Gilles Guillon, L. L. Cheng, M. Ben Mimoun, M. J. Voirol, Rolf C. Gaillard, Mauro Giacomini, Nga Ching Wo, Miriam Andrés, Maurice Manning |
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| Rok vydání: | 2002 |
| Předmět: |
Agonist
Receptors Vasopressin endocrine system Vasopressin medicine.medical_specialty Corticotropin-Releasing Hormone medicine.drug_class Gene Expression CHO Cells Biology Transfection Catecholamines Endocrinology Adrenocorticotropic Hormone Pituitary Gland Anterior Cricetinae Arginine vasopressin receptor 2 Internal medicine medicine Animals Humans Rats Wistar Receptor Cells Cultured Vasopressin receptor Arginine vasopressin receptor 1B Oxytocin receptor Diuresis Rats Arginine Vasopressin Oxytocin Receptors Oxytocin Chromaffin System Cattle Female Corticosterone hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Endocrinology. 143:4655-4664 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | To date, there are no vasopressin (VP) agonists that exhibit a high affinity and selectivity for the VP V1b receptor with respect to the V1a, V2, and oxytocin receptors. In this study, we describe the synthesis and pharmacological properties of [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP). Binding experiments performed on various membrane preparations revealed that d[Cha(4)]AVP exhibits a nanomolar affinity for V1b receptors from various mammalian species (rat, bovine, human). It exhibits high V1b/V1a and V1b/oxytocin selectivity for rat, human, and bovine receptors. Furthermore, it exhibits high V1b/V2 specificity for both bovine and human vasopressin receptors. Functional studies performed on biological models that naturally express V1b receptors indicate that d[Cha4]AVP is an agonist. Like VP, it stimulated basal and corticotropin-releasing factor-stimulated ACTH secretion and basal catecholamine release from rat anterior pituitary and bovine chromaffin cells, respectively. In vivo experiments performed in rat revealed that d[Cha4]AVP was able to stimulate both ACTH and corticosterone secretion and exhibits negligible vasopressor activity. It retains about 30% of the antidiuretic activity of VP. This long-sought selective VP V1b receptor ligand with nanomolar affinity will allow a better understanding of V1b-mediated VP physiological effects and is a promising new tool for V1b receptor structure-function studies. |
| Databáze: | OpenAIRE |
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