guanosine-triphosphate and Diabetes-Insipidus

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder characterized by renal resistance to the antidiuretic hormonal action of vasopressin. This study describes the molecular basis of nephrogenic diabetes insipidus in a dog family. Kidney membranes prepared from NDI-affected male huskies were examined for vasopressin binding and response. Compared to membranes from unaffected canines, those from the kidney inner medulla of NDI-dogs possessed normal V2-receptor numbers, but with 10-fold lower affinity for [Arg8] vasopressin (AVP). Adenylate cyclase stimulation by AVP in contrast to that by forskolin or GTP-analogues was similarly reduced in a dose responsive manner. The NDI-affected dogs showed antidiuretic responses to very high doses of V2-specific agonists, consistent with their possessing V2-receptors of lower affinity. Prolonged treatment with V2-agonists, 1-deamino [D-Arg8] VP (dDAVP) and 1-deamino [Val4, Sar7] AVP (dVSAVP), rendered the NDI-affected dogs near normal in terms of water intake and urine osmolality.

Topics: Adenylyl Cyclases; Animals; Arginine Vasopressin; Binding, Competitive; Cell Membrane; Colforsin; Diabetes Insipidus; Dogs; GTP-Binding Proteins; Guanosine Triphosphate; Male; Radioligand Assay; Receptors, Angiotensin; Receptors, Vasopressin; Sodium Fluoride

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Angiotensin II; Animals; Calcitonin; Cell Membrane; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Guanosine Triphosphate; Hormones; Isoproterenol; Kidney; Kidney Tubules; Magnesium; Male; Norepinephrine; Oxytocin; Parathyroid Hormone; Prostaglandins; Rats; Vasopressins; Water