Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor

Allotopic antagonism of the non-peptide atrial natriuretic peptide (ANP) antagonist HS-142-1 on natriuretic peptide receptor NPR-A

“…In agreement with previous reports indicating that HS-142-1 has affinity for NPR-A and NPR-B but not for the NPR-C, angiotensin II or endothelin receptors [9], we found no competitive interaction of HS-142-1 with ANP binding to the NPR-C receptor (Figure 4). Since the NPR-C receptor is a dimer devoid of any guanylate cyclase activity, we then tested the role of the dimeric structure of the receptor.…”

“…Our studies with the NPR-C receptor confirm earlier observations that HS-142-1 does not bind to the NPR-C receptor. Morishita et al [9] reported that 20 % of the specific binding of "#&I-ANP was not competed by HS-142-1 in a preparation containing all three NPRs. Following purification of the receptor preparation with GTP-agarose, all the HS-142-1-resistant binding disappeared.…”

“…In these studies it was found that HS-142-1 inhibited the binding of "#&I-ANP to the NPR-A in a dose-dependent manner with an IC &! of 0.9 µg\ml [9]. In another study they found that HS-142-1 also inhibited the production of cGMP in cells containing NPR-A and NPR-B with an IC &!…”

“…HS-142-1 is a novel microbial polysaccharide which was isolated from the culture broth of Aureobasidium sp. [9]. HS-142-1 is a mixture of 20-30 kinds of linear β-1,6-glucan esterified by caproic acid, differing in the number of glucose residues (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and the degree of esterification by caproic acid [9].…”

Ligand-gated Ion Channels

“…coli heat-stable enterotoxin (STa), linaclotide (Harris and Crowell, 2007) Selective antagonists A71915 (9.2-9.5, Delporte et al, 1991), [Asu7,23′]-b-ANP 7-28 (7.5, Kambayashi et al, 1989), anantin (Wyss et al, 1991) Monoclonal antibody 3G12 (Drewett et al, 1995), [Ser 11 ](N-CNP,C-ANP)pBNP 2-25 (Deschenes et al, 2005) AP811 ( The polysaccharide obtained from fermentation of Aureobasidium species, HS142-1, acts as an antagonist at both NPR-A and NPR-B receptors (Morishita et al, 1991).…”