C-TYPE NATRIURETIC PEPTIDE AND BRAIN NATRIURETIC PEPTIDE INHIBIT ADENYLYL-CYCLASE ACTIVITY - INTERACTION WITH ANF-R2 ANP-C RECEPTORS/

C-type natriuretic peptide (CNP) and brain natriuretic peptide (BNP) a re members of the natriuretic peptide family, which have been shown to interact with ANP-C/ANF-R2 receptors in addition to ANP-B receptor su btypes. The present study was undertaken to investigate if the interac tion of CNP and BNP with ANP-C receptors results in the inhibition of adenylyl cyclase activity. CNP and BNP inhibited adenylyl cyclase acti vity in heart and brain striatal membranes in a concentration dependen t manner with an apparent K-i between 0.1 and 1.0 nM. Maximal inhibiti on observed in heart membranes were about 25% and 35% for BNP and CNP respectively however the inhibitions in brain striatal membranes were smaller ( similar to 20%). The inhibition was dependent on the presenc e of guanine nucleotides and was attenuated by pertussis toxin treatme nt, In addition, CNP inhibited the stimulatory effect of isoproterenol on adenylyl cyclase, whereas CNP as well as BNP shelved an additive e ffect with the inhibitory response of angiotensin II on adenylyl cycla se activity, When the combined effect of C-ANF(4-23)/BNP, C-ANF(4-23)/ CNP and BNP/CNP at optimal concentrations was studied together on aden ylyl cyclase activity, the percent inhibition remained the same for C- ANF(4-23) and BNP or C-ANF(4-23) and CNP, however, an additive inhibit ory effect was observed for BNP and CNP, These results suggest that CN P and BNP like C-ANF(4-23), interact with ANP-C receptors and result i n the inhibition of adenylyl cyclase activity, On the other hand, CNP and BNP interact with the ANP-C receptor, however, the interaction may be at different sites or there may be two subpopulations of ANP-C rec eptors specific for each of the peptides, These results indicate that BNP and CNP, like ANP and C-ANF(4-23), inhibit the adenylyl cyclase/cA MP signal transduction system through an inhibitory guanine nucleotide regulatory protein, by interacting with ANP-C receptor subtypes.