Details
Zusammenfassung: <jats:p>In the presence of 1 μM atrial natriuretic factor (ANF) and low (0.1 mM) Mg<jats:sup>2+</jats:sup> concentrations, the initial rate of binding of [<jats:sup>3</jats:sup>H]guanosine 5′‐[β,γ‐imido)triphosphate ([<jats:sup>3</jats:sup>H]p[NH]ppG) to rat lung plasma membranes was increased twofold to threefold. ANF‐dependent stimulation of the initial rate of [<jats:sup>3</jats:sup>H]p[NH]ppG binding was reduced at high (5 mM) Mg<jats:sup>2+</jats:sup> concentrations. Preincubation of membranes with p[NH]ppG (5 min at 37°C) eliminated the ANF‐dependent effect on [<jats:sup>3</jats:sup>H]p[NH]ppG binding whereas ANF‐dependent [<jats:sup>3</jats:sup>H]p[NH]ppG binding was unaffected by similar pretreatment with guanosine 5′‐[β‐thio]diphosphate (GDP[βS]). An increase in ANF concentration from 10 pM to 1 μM caused a 40% decrease in forskolin‐stimulated or isoproterenol‐stimulated adenylate cyclase activities (IC<jats:sub>50</jats:sub> 5 nM) in rat lung plasma membranes. GTP (100 μM) was obligatory for the ANF‐dependent inhibition of adenylate cyclase, which could be completely overcome by the presence of 100 μM GDP[βS] or the addition of 10 mM Mn<jats:sup>2+</jats:sup>. Reduction of Na<jats:sup>2+</jats:sup> concentration from 120 mM to 20 mM had the same effect. Pertussis toxin eliminated ANF‐dependent inhibition of adenylate cyclase by catalyzing ADP‐ribosylation of membrane‐bound N<jats:sub>i</jats:sub> protein (41‐kDa α subunit of the inhibitory guanyl‐nucleotide‐binding protein of adenylate cyclase). The data support the notion that one of the ANF receptors in rat lung plasma membranes is negatively coupled to a hormone‐sensitive adenylate cyclase complex via the GTP‐binding N<jats:sub>i</jats:sub> protein.</jats:p>
Umfang: 531-535
ISSN: 0014-2956
1432-1033
DOI: 10.1111/j.1432-1033.1988.tb14131.x