Urodilatin and β-ANF: Binding properties and activation of particulate guanylate cyclase

Urodilatin (ANF-(95–126)) and β-ANF, the antiparallel dimer of ANF-(99–126), are naturally occurring members of the ANF family. We studied their receptor binding properties in human platelets and Triton-solubilized membranes from bovine adrenal cortex and their ability to activate particulate guanylate cyclase in bovine adrenal cortex. In human platelets containing R 2-receptors not coupled to particulate guanylate cyclase urodilatin binds with similar affinity as ANF-(99–126) (K D: 55 pM), whereas β-ANF has an affinity lower than the truncated ANF-(103–123) (K D: 295 pM and 154 pM). Scatchard analysis indicates one binding site for urodilatin as well as for β-ANF. In adrenal cortex containing predominantly R 1-receptors coupled to particulate guanylate cyclase, urodilatin binds with a higher affinity (K D: 30 pM) than ANF-(99–126) (K D: 52 pM) and stimulates to a similar extent to ANF-(99–126) (about twofold at 1 μM), whereas β-ANF has a smaller affinity (K D: 120 pM) and stimulates particulate guanylate cyclase to a lower extent than ANF-(99–126). The data from platelets and adrenal cortex show that β-ANF has low binding affinities but stimulates particulate guanylate cyclase, whereas urodilatin appears to be a physiological R 1-agonist.