Down-regulation of vasopressin V1a receptor mRNA in diabetes mellitus in the rat

1. To investigate the mechanism of hepatic V1a vasopressin receptor down- regulation in streptozotocin-induced diabetes mellitus in the rat, we measured hepatic V1a receptor mRNA by in situ hybridization histochemistry using oligonucleotide probes to the V1a receptor and Northern blotting. 2. Diabetes mellitus caused hyperglycaemia, hyperosmolality and increased plasma vasopressin concentrations (P<0.01). Hepatocyte V1a receptor mRNA was reduced by 76% in diabetic rats (P<0.01) and by 53% in insulin-treated diabetic rats (P<0.01) versus control rats, in parallel with reduced V1a radioligand binding and vasopressin-stimulated inositol phosphates production. There was a similar decrease in hepatic V1a/18S mRNA density ratio in the diabetic and diabetic+insulin groups (both P<0.05 versus control). 3. These findings suggest that altered V1a mRNA transcription is responsible for the reduced hepatic V1a receptor density in diabetes mellitus.