DOWN-REGULATION OF VASOPRESSIN V1A RECEPTOR MESSENGER-RNA IN DIABETES-MELLITUS IN THE RAT

1.To investigate the mechanism of hepatic Via vasopressin receptor dow n-regulation in streptozotocin-induced diabetes mellitus in the rat, w e measured hepatic V1a receptor mRNA by in situ hybridization histoche mistry using oligonucleotide probes to the V1a receptor and Northern b lotting. 2. Diabetes mellitus caused hyperglycaemia, hyperosmolality a nd increased plasma vasopressin concentrations (P<0,01), Hepatoycte Vi a receptor mRNA was reduced by 76% in diabetic rats (P< 0.01) and by 5 3% in insulin-treated diabetic rats (P<0,01) versus control rats, in p arallel with reduced Via radioligand binding and vasopressin-stimulate d inositol phosphates production, There was a similar decrease in hepa tic V1a/18S mRNA density ratio in the diabetic and diabetic+insulin gr oups (both P<0,05 versus control). 3. These findings suggest that alte red V1a mRNA transcription is responsible for the reduced hepatic V1a receptor density in diabetes mellitus.