Urodilatin and beta-ANF: binding properties and activation of particulate guanylate cyclase

Urodilatin (ANF-(95-126] and beta-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 R2-receptors not coupled to particulate guanylate cyclase urodilatin binds with similar affinity as ANF-(99-126) (KD: 55 pM), whereas beta-ANF has an affinity lower than the truncated ANF-(103-123) (KD: 295 pM and 154 pM). Scatchard analysis indicates one binding site for urodilatin as well as for beta-ANF. In adrenal cortex containing predominantly R1-receptors coupled to particulate guanylate cyclase, urodilatin binds with a higher affinity (KD: 30 pM) than ANF-(99-126) (KD: 52 pM) and stimulates to a similar extent to ANF-(99-126) (about two fold at 1 muM), whereas beta-ANF has a smaller affinity (KD: 120 pM) and stimulates particulate guanylate cyclase to a lower extent than ANF-(99-126). The data from platelets and adrenal cortex show that beta-ANF has low binding affinities but stimulates particulate guanylate cyclase, whereas urodilatin appears to be a physiological R1-agonist.