The Effect of U-50488H, on Vasopressin Receptor Expression in Immature Ovine Kidney and Brainstem

Date
2014-05-02
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Abstract
Activation of kappa opioid receptors (KORs) by the naturally occurring ligand, dynorphin A, or KOR agonists such as U-50488H (a selective KOR agonist) is well documented to elicit a diuretic response in different animal species. However, the mechanism(s) underlying the aquaretic effect of U-50488H is not yet well understood. It is thought that KORs activation modulates the plasma level of arginine vasopressin (AVP). AVP is well known as an antidiuretic hormone (ADH) because its main effect on the kidney is to decrease urine flow. AVP exerts its biological effects via activation of at least three specific G-protein coupled receptors: V1Rs, V2Rs and V3Rs. V1Rs are mainly expressed in brain and vascular smooth muscle cells, and V2Rs are mainly expressed in the kidney. A functional relationship between the kappa opioid system and the vasopressinergic system has been suggested in the literature. However, no previous investigation has been attempted to investigate this relationship at the receptor level. The first objective of this investigation was to describe for the first time, mRNA and protein expression of V1Rs and V2Rs in immature ovine brainstem and kidney using highly sensitive, accurate, reproducible RT-qPCR and semi-quantitive Westren Blot analysis respectively. The second objective was to assess whether V1R and V2R expression is regulated by repeated stimulation of KORs by U-50488H administration. Results from these investigations demonstrate for the first time the regional variations in V1R and V2R mRNA and protein level between brainstem and kidney of six-week-old sheep as well as regional variation of the effect of KOR activation on V1R and V2R expression at both transcriptional and translational levels
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Physiology
Citation
Mutardi, M. (2014). The Effect of U-50488H, on Vasopressin Receptor Expression in Immature Ovine Kidney and Brainstem (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28092