Characteristics of dendroaspis natriuretic peptide and its receptor in streptozotocininduced diabetic rats

Dendroaspis natriuretic peptide (DNP) shares a functionally important sequence homology with other natriuretic peptides. However, the characteristics of DNP and its receptor in the context of diabetes remafin to be fully elucidated. In the present study, alterations in the plasma levels and tissue contents of DNP and the properties of its receptor in diabetic rats, induced by streptozotocin (STZ) injection, were investigated. The plasma levels of DNP were 90.01±4.12 and 196.68±5.60 pg/ml in the control and STZinduced diabetic rats, respectively. The tissue contents of DNP in the cardiac atrium, ventricle, renal cortex and inner medulla of the STZinduced diabetic rats were also significantly increased compared with the control rats. Specific 125IDNPbinding sites were located predominantly in the glomeruli and inner medulla of the rat kidney. In the glomeruli of the kidney, the apparent dissociation constants (Kd) of 125IDNP in the control and STZinduced diabetic rats were 0.41±0.03 and 0.56±0.06 nM, respectively. The maximum binding capacities (Bmax) of 125IDNP in control and STZinduced diabetic rats were 2.98±0.21 and 6.22±1.06 fmol/mg protein, respectively. However, no differences were observed in the apparent Kd and Bmax of 125IDNP in the inner medulla of the kidney between the control and STZinduced diabetic rats. In the glomerular and inner medullary kidney membranes, DNP stimulated the production of cyclic guanosine monophosphate (cGMP) in a dosedependent manner. The magnitude of cGMP production in glomerular membranes was greater in the STZinduced diabetic rats, whereas the magnitude of cGMP production in the inner medullary membranes was lower in the STZinduced diabetic rats compared with the control rats. These results indicated that STZinduced diabetes modulate DNP and its receptor, and also suggested that modulation of the DNP system is involved in the renal function of diabetic animals via the intracellular domain of the kidney NP receptor.