Date of Award

5-2011

Degree Type

Restricted Access Thesis

Degree Name

Master of Science

Field of Study

Cardiovascular Science

Department

Graduate School of Biomedical Sciences

First Advisor

Tom Cunningham

Abstract

Secretin (SCT) exists in the hypothalamo-neurohypophysis axis of the rat. Secretin receptor null mice show altered glomerular and renal tubular morphology along with mild polydipsia and polyuria. We hypothesize SCT may play a role in the physiology of water regulation in the rat. Water deprivation (WD) and bile duct ligation (BDL) models were used. Rats were WD for 48 h and rehydrated with either water (RH+W) or 0.9% NaCl (RH+S) for 2 h before sacrifice. Sham and BDL rats were sacrificed 4 weeks after surgery. The presence of SCT and arginine-vasopressin (AVP) in the pituitary; secretin receptor (SCTR), vasopressin receptor 2 (AVP2R), and aquaporin-2 water channel (AQP-2) in the kidney were analyzed using the Western blot technique. Plasma SCT concentrations were measured by enzyme immunoassay (EIA) analysis. Our results show that there is no change in pituitary SCT content in WD rats when compared to controls or in the BDL model. There is also no change in AVP content in either model. No change occurred in plasma SCT concentration for either model. AVP2R and SCTR (at 50kDa) are significantly decreased in the BDL group compared to sham (P<0.015; P<0.004 respectively). Abundance of glycosylated and non-glycosylated AQP-2 are increased significantly for RH+W and RH+S compared to control (P<0.002; P<0.015 respectively), but neither showed a difference between sham and BDL groups. We confirm the presence of SCT in the neurohypophysis, but do not support the hypothesis that SCT acts independently of AVP to regulate water absorption in response to homeostatic challenges or disease models with increased AVP. We also show decreased abundance of the SCTR in the kidney of a model of dilutional hyponatremia in the rat.

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