Vasopressin V1 and V2 receptors in diabetes mellitus.
Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.
Trinder
D
D
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Phillips
P A
PA
Stephenson
J M
JM
Risvanis
J
J
Aminian
A
A
Adam
W
W
Cooper
M
M
Johnston
C I
CI
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism*; D015290:Second Messenger Systems
D001786:Blood Glucose; D007295:Inositol Phosphates; D007328:Insulin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000242:Cyclic AMP